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Time trial performance in normal and high ambient temperature: Is there a role for 5-HT?
Abstract
The original central fatigue hypothesis suggested that fatigue during prolonged exercise might be due to higher 5-HT activity. Therefore, we examined the effects of acute administration of a selective 5-HT reuptake inhibitor (SSRI) on performance and thermoregulation. Eleven healthy trained male cyclists completed four experimental trials (two in 18°C, two in 30°C) in a double-blind randomised crossover design. Subjects ingested either a placebo (PLA: lactose 2 × 10 mg) or citalopram (CITAL 2 × 10 mg) on the evening before and the morning of the trial. Subjects cycled for 60 min at 55% W
max, immediately followed by a time trial (TT) to measure performance. The significance level was set at P < 0.05. Acute SSRI did not significantly change performance on the TT (18°C P = 0.518; 30°C P = 0.112). During recovery at 30°C, core temperature was significantly lower in the CITAL trial (P < 0.012). At 30°C heart rate was significantly lower after exercise in CITAL (P = 0.013). CITAL significantly increased cortisol concentrations at rest (P = 0.016), after the TT (P = 0.006) and after 15-min recovery (P = 0.041) at 30°C. 5-HT reuptake inhibition did not cause significant reductions in performance. Core temperature was significantly lower only after the time trial in heat after CITAL administration. The present work failed to prove whether or not 5-HT has an exclusive role in the onset of centrally mediated fatigue during prolonged exercise in both normal and high ambient temperature.
... In normal ambient temperatures the effects on performance are, however, not straightfoward (Meeusen et al., 2006b;Roelands & Meeusen, 2010). Some early studies observed a negative effect of an increase in 5-HT concentration on performance (Wilson & Maughan, 1992;Strüder et al., 1998), while others could not confirm that finding (Meeusen et al., 2001;Roelands et al., 2009a). A very recent study showed that one factor that might influence the response to a 5-HT challenge is the training level of the subject. ...
... Teixeira-Coelho et al. (2014) showed that performance in a time-to-exhaustion trial was significantly decreased after administration of paroxetine (a selective 5-HT reuptake inhibitor), only in the group with higher aerobic capacity [PL 3 according to De Pauw et al. (2013a)] and not in the group with a lower aerobic capacity (PL 1). The results probably only reflect the training status of the subjects in this specific study because in the study by Roelands et al. (2009a), the training level of the subjects was identical, whereas it was even higher in the Meeusen et al. (2001) paper (PL 4). However, in these studies, different drugs were used (respectively, citalopram and fluoxetine: selective 5-HT reuptake inhibitors), indicating that these results could also be "drug-specific." ...
... A study in our lab (Roelands et al., 2009a) used a protocol consisting of a 60-min fixed intensity exercise (55% Wmax) followed by a preloaded time trial in 30°C. This time trial was started with a resistance corresponding to 75% Wmax, but subjects were free to change power output from the onset of exercise. ...
Fatigue during prolonged exercise is a multifactorial phenomenon. The complex interplay between factors originating from both the periphery and the brain will determine the onset of fatigue. In recent years, electrophysiological and imaging tools have been fine-tuned, allowing for an improved understanding of what happens in the brain. In the first part of the review, we present literature that studied the changes in electrocortical activity during and after exercise in normal and high ambient temperature. In general, exercise in a thermo-neutral environment or at light to moderate intensity increases the activity in the β frequency range, while exercising at high intensity or in the heat reduces β activity. In the second part, we review literature that manipulated brain neurotransmission, through either pharmacological or nutritional means, during exercise in the heat. The dominant outcomes were that manipulations changing brain dopamine concentration have the potential to delay fatigue, while the manipulation of serotonin had no effect and noradrenaline reuptake inhibition was detrimental for performance in the heat. Research on the effects of neurotransmitter manipulations on brain activity during or after exercise is scarce. The combination of brain imaging techniques with electrophysiological measures presents one of the major future challenges in exercise physiology/neurophysiology.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
... In running rats, a central injection of tryptophan, which is the amino acid precursor for 5-HT synthesis, increases the heat storage rate and decreases mechanical efficiency, thereby accelerating fatigue during submaximal exercise (Cordeiro et al., 2014;Soares et al., 2003;. The contribution of serotonergic function to fatigue mechanisms has also been investigated using pharmacological tools in human studies (Bridge et al., 2003;Marvin et al., 1997;Meeusen et al. 1997;2001;Roelands et al., 2009). However, some of the tested drugs, such as buspirone, are non-selective agonists of 5-HT receptors; therefore, caution is required when interpreting the outcomes from these studies based on exclusive changes in the serotonergic system. ...
... Physical training decreased the ergolytic effect caused by the central administration of a 5-HT agonist, which suggests decreased sensitivity in trained animals. Because the evidence generated for a role of 5-HT in fatigue in rodents could not be consistently reproduced in human studies (Roelands et al., 2009), it is important to investigate whether the sensitivity of the 5-HT system is affected by aerobic capacity in exercising subjects. ...
... Our experiments provide the first measurements of the sensitivity of the brain serotonergic system in exercising humans, in contrast to the measurements obtained during resting conditions in past investigations (Jakeman et al., 1994;Broocks et al., 1999). Considering that brain 5-HT is usually associated with decreased physical performance (Wilson and Maughan, 1992) or no changes at all (Roelands et al., 2009), our results are counterintuitive because they suggest increased sensitivity to 5-HT in individuals with higher conditioning. An interesting hypothesis to be tested in future studies is whether the sensitivity of the dopaminergic/noradrenergic systems also differs in exercising subjects with different aerobic capacities. ...
This study investigated the influence of aerobic capacity on the activation of the central serotonergic system and exercise fatigue in young men that ingested a selective serotonin reuptake inhibitor and were then subjected to moderate-intensity physical exercise. The maximal oxygen consumption of sixteen volunteers was measured during an incremental test. The volunteers were divided into two groups: subjects with higher (HAC) and lower (LAC) aerobic capacities. The volunteers were subjected to four experimental trials in which they ingested either placebo or paroxetine (10, 20 or 40 mg) and, 4.5 h later, cycled at 60% of their maximal power output until reaching fatigue. None of the three paroxetine doses influenced the total exercise time in the LAC group. However, for the HAC group, the time to fatigue in the 20 mg paroxetine condition was 15% less than that in the placebo condition (76.3 ± 5.1 min vs. 90.0 ± 7.9 min; p < 0.05). The time to fatigue was higher in the HAC group than in the LAC group for all treatments. Our results provide additional evidence that aerobic capacity modulates the activity of the serotonergic system. However, contrary to what would be expected considering previous reports, the activation of the serotonergic system in exercising subjects in the HAC group was not less than that in the LAC group.
... The data led to the hypothesis that elevated serotonin content may contribute to poor exercise performance during periods of excessive training. A special focus has been given to the pharmacological manipulations used to elucidate the relationship between increased serotonergic activity and the early onset of fatigue (Bailey et al., 1993;Roelands et al., 2009). A study by Bailey et al. (1993) demonstrated that exercise performance benefitted from the use of a serotonin antagonist, while treatment with a serotonin agonist led to a detriment in exercise performance. ...
... However, the results are contradictory and inconclusive. Although data have demonstrated no effect of different serotonin reuptake inhibitors (pizotifen, fluoxetine, citalopam) on exercise performance in humans (Meeusen et al., 2001;Pannier et al., 1995;Parise et al., 2001;Roelands et al., 2009;Strachan et al., 2004), findings from Struder et al. (1998) and W. M. Wilson et al. (1992) indicate that fatigue occurs sooner with pharmacological augmentation of the brain's serotonergic activity by serotonin re-uptake inhibitor (paroxetine) supplements. These different outcomes might be explained by divergent exercise protocols, pharmacological manipulations, drug receptor specificity and drug dosages. ...
... During exercise, the acute ingestion of the drug in humans has been shown to improve time-trial exercise performance in a warm environment, despite higher body temperatures (Watson et al., 2005). In contrast to acute bupropion administration, the chronic ingestion of the drug does not influence time-trial exercise performance under the same environmental conditions, aside from inducing lower body temperature values than the temperatures observed during the acute bupropion study (Roelands et al., 2009;Watson et al., 2005). The mechanism for these observed discrepancies in bupropion administration seems to be the possible adaptation of central neurotransmitter homeostases during the treatment (Roelands et al., 2009). ...
... End-spurt. In accordance with well-known field observations and as previously described in the literature (Roelands et al., 2009) our results indicated a characteristic end-spurt phenomenon in the last 10-15% of the time-trial. This end-spurt was seen whatever the condition ( Figure 1B). ...
... This end-spurt was seen whatever the condition ( Figure 1B). Our results confirm that the subjects have the drive and/or motivation to augment power output when approaching the end-point in normoxia but also in hypoxia (what is not the case anymore after administration of a serotonin reuptake inhibitor in normoxia) (Roelands et al., 2009). ...
Purpose: Hypoxia is one major environmental factor, supposed to mediate central motor command as well as afferent feedbacks at rest and during exercise. By using a comparison of normobaric (NH) and hypobaric (HH) hypoxia with the same ambient pressure in oxygen, we examined the potential differences on the cerebrovascular and muscular regulation interplay during a self-paced aerobic exercise.
Methods: Sixteen healthy subjects performed three cycling time-trials (250 kJ) in three conditions: HH, NH and normobaric normoxia (NN) after 24 h of exposure. Cerebral and muscular oxygenation were assessed by near-infrared spectroscopy, cerebral blood flow by Doppler ultrasound system. Gas exchanges, peripheral oxygen saturation, power output and associated pacing strategies were also continuously assessed.
Results: The cerebral oxygen delivery was lower in hypoxia than in NN but decreased similarly in both hypoxic conditions. Overall performance and pacing were significantly more down-regulated in HH versus NH, in conjunction with more impaired systemic (e.g . saturation and cerebral blood flow) and prefrontal cortex oxygenation during exercise.
Conclusions: The difference in pacing was likely the consequence of a complex interplay between systemic alterations and cerebral oxygenation observed in HH compared to NH, aiming to maintain an equivalent cerebral oxygen delivery despite higher adaptive cost (lower absolute power output for the same relative exercise intensity) in HH compared to NH.
... 40,41 Exercise fatigue can be quantified across a range of task modalities including repeated maximum isometric contractions and submaximal dynamic contractions. [42][43][44] Application of electrophysiological measurements during such tasks 45,46 can delineate contributions of myoelectrical failure to force loss. 36 However, these methods are limited in usefulness as they quantify fatigue during laboratory-based exercise tasks and it is largely unknown how this relates to real world performance. ...
... 198 Similarly, it is hypothesised that increased cerebral tryptophan uptake during prolonged exercise due to tryptophan displacement from albumin 199 and elevated BCAA oxidation 200 increases serotonergic activity, causing fatigue. 196,201,202 However, SSRI treatment demonstrates inconsistent effects on exercise fatigue, 43,203 and the time to exercise exhaustion was consistent between subjects ingesting tryptophan or BCAA 204 ; these collective findings dispute the serotonin hypotheses. ...
Background:
Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of patients with mild to inactive disease. Fatigue is the commonest reason for work absence in IBD, and patients often report fatigue burden to be greater than that of primary disease symptoms. Relatively few evidence-based treatment options exist, and the aetiology is poorly understood.
Aim:
To review the available data and suggest a possible aetiology of IBD fatigue and to consider the efficacy of existing management strategies and highlight potential future interventions.
Methods:
We reviewed fatigue-related literature in IBD using PubMed database.
Results:
Disease related factors such as inflammation and pharmacological treatments negatively impact skeletal muscle and brain physiology, likely contributing to fatigue symptoms. Secondary factors such as malnutrition, anaemia, sleep disturbance and psychological comorbidity are potential determinants. Immune profile, faecal microbiota composition and physical fitness differ significantly between fatigued and non-fatigued patients, suggesting these may be aetiological factors. Solution-focused therapy, high-dosage thiamine supplementation and biological therapy may reduce fatigue perception in IBD. The effect of physical activity interventions is inconclusive.
Conclusions:
A multimodal approach is likely required to treat IBD fatigue. Established reversible factors like anaemia, micronutrient deficiencies and active disease should initially be resolved. Psychosocial intervention shows potential efficacy in reducing fatigue perception in quiescent disease. Restoring physical deconditioning by exercise training intervention may further improve fatigue burden.
... Some studies Wilson & Maughan, 1992) diagnosed reduced performance after administration of paroxetine and fluoxetine (reuptake inhibitors of 5-HT). However, most studies (Pannier, Bouckaert, & Lefebvre, 1995;Parise, Bosman, Boecker, Barry, & Tarnopolssky, 2001;Roelands et al., 2009) couldn't confirm these findings. Strüder and Weicker (2001) suggested the reduced performance capacity occurred after acute administration of 5-HT reuptake inhibitors may be as a result of the reduced functional capacity of 5-HT as a multipurpose generator that provides adaptability of neural network to address the needs of the central critical demands, not because of the increased activity of 5-HT. ...
... Furthermore, microinjection of apomorphine (an agonist of DA) into the hypothalamus of rat creates a DA mediated fall of temperature (Brown, Gisolf, & Mora, 1982). Besides, DA release in PO/AH during the treadmill exercise was risen , and DA caused to the increased temperature of the rats body (Myers & Yaksh, 1968), It can be expected that changes in the concentration of these neurotransmitters, helps to the changes in temperature regulation because of fatigue, especially when the exercise is being done in the hot environment (Roelands et al., 2009). ...
An exercise-induced reduction in maximal force production, or the inability to continue an activity with enough force, is defined as fatigue. Although the etiology of fatigue is complex, it can be divided into two distinct components: central and peripheral. Central fatigue is the progressive exercise-induced loss of the voluntary activation, or decrease in the neural stimulation, of the muscle, thereby reducing maximal force production. Considering the different mechanisms of strength and endurance activities as well as previous research, the authors suggest that there is peripheral fatigue in both kinds of activities. However, the mechanisms of fatigue and the rate of perceived exertion are distinct (mentally, endurance exercise is more difficult). An analysis of fatigue kinetics shows that peripheral fatigue occurs initially, and the central nervous system tries to prevent the disorder via output force through the perceptions of the metabolic condition of the muscle and the activation of additional motor units. Once peripheral fatigue surpasses a certain amount, the central nervous system reduces the number of activated motor units to prevent serious disorders in homeostasis and muscle damage, and protects the central governor. Still, in important and critical situations such as the final stages of running a marathon (when the last flight of runners is observed) and fight-or-flight situations in which someone faces a worse outcome if a task is abandoned, humans can choose one of worse or the worst alternatives to write their final destiny.
... For example, it has been suggested from animal studies that an increased serotonergic activity (29) and the ratio of serotonin to dopamine brain content during exercise (6) may be important for the development of central fatigue. However, several pharmacological studies performed in humans failed to alter the exercise capacity through changes in serotonergic neurotransmission (32), suggesting that the role of serotonin is often overestimated and dependent on drug dosages and receptor that is targeted (25). Other investigations reported that pharmacologically induced inhibition of the reuptake of dopamine and noradrenaline led to changes in performance in both normal (12,33) and high ambient temperatures (30,33,34). ...
... The time trial (TT) protocol applied (see description in the succeeding part of this article) has been shown to be much more reliable and reproducible than a constant load exercise sustained to exhaustion, especially in well-trained subjects (14). Therefore, the subjects selected for this experiment had an experience of at least 5 yr of regular cycling training and competition that ensured a high degree of reproducibility of performance across the different trials (14,(32)(33)(34). Because of potential issues with the menstrual cycle and hormonal variations in female subjects, experiments were only performed on a male population. ...
Purpose:
Prolonged exhaustive exercise induces a failure of the nervous system to activate the involved muscles maximally (i.e., central fatigue). Part of central fatigue may reflect insufficient output from the motor cortex (i.e., supraspinal fatigue), but the cause is unresolved. To investigate the potential link between supraspinal fatigue and changes in brain concentration of dopamine and noradrenaline in temperate environment, we combined neurophysiological methods and pharmacological manipulation of these two neurotransmitters.
Methods:
Changes in performance of a cycling exercise (time trial [TT]) were tested after oral administration of placebo (Pla), dopamine, or noradrenaline reuptake inhibitors (methylphenidate and reboxetine [Rebox], respectively) in well-trained male subjects. Changes in voluntary activation, corticospinal excitability, and muscle contractile properties were tested in the knee extensors using transcranial magnetic stimulation and motor nerve electrical stimulation before and after exercise. A psychomotor vigilance task (PVT) was also performed.
Results:
Compared with Pla, methylphenidate did not affect exercise performance (P = 0.19), but more time was needed to complete the TT after administration of Rebox (approximately 9%, P < 0.05). For the latter condition, the reduced performance was accompanied by a central/supraspinal fatigue (5%-6%, P < 0.05) and worsened PVT performance (7%, P < 0.05). For the three conditions, corticospinal excitability was unchanged, and peripheral fatigue was similar. Because the ingestion of Rebox induced a greater decrease in voluntary activation and PVT performance after the TT than Pla, with no modification in corticospinal excitability, the noradrenaline reuptake inhibitor likely affected supraspinal circuits located before the motor cortex.
Conclusion:
These results suggest that noradrenaline, but not dopamine reuptake inhibition, contributes to the development of central/supraspinal fatigue after a prolonged cycling exercise performed in temperate conditions.
... It was postulated that this mechanism could influence the perception of effort and, therefore, fatigue (Newsholme & Blomstrand, 2006;Newsholme et al., 1987). Following this original hypothesis, several studies used pharmacological interventions to modify CNS 5-HT levels during prolonged cycling, and found that cycling performance was sometimes (Meeusen et al., 2001;Roelands et al., 2009;Strachan et al., 2004), but not always (Strüder et al., 1998;Teixeira-Coelho et al., 2014;Wilson & Maughan, 1992), limited by enhanced 5-HT concentrations. These mixed findings are most likely a reflection on the complexity of neurotransmitter systems, and no single neurotransmitter is responsible for exercise-induced central fatigue. ...
Ionotropic inputs to motoneurones have the capacity to depolarise and hyperpolarise the motoneurone, whereas neuromodulatory inputs control the state of excitability of the motoneurone. Intracellular recordings of motoneurones from in vitro and in situ animal preparations have provided extraordinary insight into the mechanisms that underpin how neuromodulators regulate neuronal excitability. However, far fewer studies have attempted to translate the findings from cellular and molecular studies into a human model. In this review, we focus on the role that serotonin (5-HT) plays in muscle activation in humans. 5-HT is a potent regulator of neuronal firing rates, which can influence the force that can be generated by muscles during voluntary contractions. We firstly outline structural and functional characteristics of the serotonergic system, and then describe how motoneurone discharge can be facilitated and suppressed depending on the 5-HT receptor subtype that is activated. We then provide a narrative on how 5-HT effects can influence voluntary activation during muscle contractions in humans, and detail how 5-HT may be a mediator of exercise-induced fatigue that arises from the central nervous system.
... [66][67][68] However, most studies have demonstrated that serotonin reuptake inhibitors do not negatively affect central fatigue. [69][70][71][72][73] For example, Meeusen et al. used a double-blind randomized crossover design to administer the serotonin reuptake inhibitor fluoxetine to athletes before exercise for 90 minutes. The results showed that exercise performance is not influenced by fluoxetine, although some plasma hormones indicated a central effect of the drug. ...
Central fatigue leads to reduced ability to perform mental tasks, disrupted social life, and impaired brain functions from childhood to old age. Regarding the neurochemical mechanism, neuroactive tryptophan metabolites are thought to play key roles in central fatigue. Previous studies have supported the “tryptophan-serotonin enhancement hypothesis” in which tryptophan uptake into extensive brain regions enhances serotonin production in the rat model of exercise-induced fatigue. However, serotonin was transiently released after 30 minutes of treadmill running to exhaustion, but this did not reflect the duration of fatigue. In addition, as the vast majority of tryptophan is metabolized along the kynurenine pathway, possible involvement of the tryptophan-kynurenine pathway in the mechanism of central fatigue induction has been pointed out. More recently, our study demonstrated that uptake of tryptophan and kynurenine derived from the peripheral circulation into the brain enhances kynurenic acid production in rat brain in sleep deprivation–induced central fatigue, but without change in serotonin activity. In particular, dynamic change in glial-neuronal interactive processes within the hypothalamus-hippocampal circuit causes central fatigue. Furthermore, increased tryptophan-kynurenine pathway activity in this circuit causes reduced memory function. This indicates a major potential role for the endogenous tryptophan-kynurenine pathway in central fatigue, which supports the “tryptophan-kynurenine enhancement hypothesis.” Here, we review research on the basic neuronal mechanism underlying central fatigue induced by neuroactive tryptophan metabolites. Notably, these basic findings could contribute to our understanding of latent mental problems associated with central fatigue.
... There was an inverse correlation between the increase in 5-HT and physical performance in the warm environment, indicating a possible role of this neurotransmitter in the fatigue process, primarily in conditions of environmental heat stress (41). However, pharmacological manipulations to change the brain 5-HT concentrations in humans have produced divergent responses, with some studies showing a decrease in performance after administration of selective serotonin reuptake inhibitors (42,43), while other studies have not observed this effect (44,45). ...
Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling that leads to reduced intensity or interruption of physical exercises, thereby regulating performance. The present review aims to present advances on the understanding of fatigue, which has recently been proposed as a defense mechanism instead of a “physiological failure” in the context of prolonged (aerobic) exercises. We also present recent advances on the association between serotonin, dopamine and fatigue. Experiments with rodents, which allow direct manipulation of brain serotonin and dopamine during exercise, clearly indicate that increased serotoninergic activity reduces performance, while increased dopaminergic activity is associated with increased performance. Nevertheless, experiments with humans, particularly those involving nutritional supplementation or pharmacological manipulations, have yielded conflicting results on the relationship between serotonin, dopamine and fatigue. The only clear and reproducible effect observed in humans is increased performance in hot environments after treatment with inhibitors of dopamine reuptake. Because the serotonergic and dopaminergic systems interact with each other, the serotonin-to-dopamine ratio seems to be more relevant for determining fatigue than analyzing or manipulating only one of the two transmitters. Finally, physical training protocols induce neuroplasticity, thus modulating the action of these neurotransmitters in order to improve physical performance.
... Increasing its concentrations resulted in decreased time trial performance (Roelands et al., 2008b). Although no effects of serotonin level manipulations on performance could be demonstrated, high serotonin levels appear to inhibit athletes' ability and motivation to perform an end sprint during exercise (Roelands et al., 2009). ...
Endurance sports are booming, with sports passionates of varying skills and expertise battering city streets and back roads on their weekly or daily exercise rounds. The investments required for performing in endurance exercise are nevertheless considerable, and passion for their sport might explain the efforts endurance athletes are willing to make. Passion may be defined as a strong motivational force and as such might be related to the neurophysiological basis underlying the drive to exercise. A complex relationship between the brain and other systems is responsible for athletes' exercise behavior and thus performance in sports. We anticipate important consequences of athletes' short term choices, for example concerning risk taking actions, on long term outcomes, such as injuries, overtraining and burnout. We propose to consider athletes' type of passion, in combination with neurophysiological parameters, as an explanatory factor in understanding the apparent disparity in the regulation of exercise intensity during endurance sports. Previous research has demonstrated that athletes can be passionate toward their sport in either a harmonious or an obsessive way. Although both lead to considerable investments and therefore often to successful performances, obsessive passion may affect athlete well-being and performance on the long run, due to the corresponding inflexible exercise behavior. In this perspective we will thus examine the influence of passion in sport on athletes' short term and long term decision-making and exercise behavior, in particular related to the regulation of exercise intensity, and discuss the expected long term effects of both types of passion for sport.
... On the one hand, Wilson and Maughan (1992), Davis, Bailey, Jackson, Strasner, and Morehouse (1993) and Strüder et al. (1998) detected performance decrements after European Journal of Sport Science 5 administration of paroxetine and fluoxetine (serotonin reuptake inhibitors). Other studies, on the other hand, were unable to reproduce this negative impact on performance capacity (Meeusen, Piacentini, Van Den Eynde, Magnus, & De Meirleir, 2001;Meeusen, Roeykens, Magnus, Keizer, & De Meirleir, 1997;Pannier, Bouckaert, & Lefebvre, 1995;Parise, Bosman, Boecker, Barry, & Tarnopolsky, 2001;Roelands, Goekint, et al., 2009). These mixed outcomes presumably result from the complexity of the serotonergic system, as many different receptors and receptor subtypes have already been identified, each with different functions and interactions (Taylor, Amann, Duchateau, Meeusen, & Rice, 2016). ...
Fatigue during exercise can be approached from different angles. Peripheral fatigue is usually described as an impairment located in the muscle and characterized by a metabolic end point, while central fatigue is defined as a failure of the central nervous system to adequately drive the muscle. The aim of the present narrative review paper is to look at the mechanisms involved in the occurrence of fatigue during prolonged exercise, predominantly from a brain neurochemical point of view. From studies in rodents it is clear that exercise increases the release of several neurotransmitters in different brain regions, and that the onset of fatigue can be manipulated when dopaminergic influx in the preoptic and anterior hypothalamus is increased, interfering with thermoregulation. This is however not as straightforward in humans, in which most studies manipulating brain neurotransmission failed to change the onset of fatigue in normal ambient temperatures. When the ambient temperature was increased, dopaminergic and combined dopaminergic and noradrenergic reuptake inhibition appeared to override a safety switch, allowing subjects to push harder and become much warmer, without changing their perception. In general, we can conclude that brain neurochemistry is clearly involved in the complex regulation of fatigue, but many other mediators also play a role.
... Increasing its concentrations resulted in decreased time trial performance (Roelands et al., 2008b). Although no effects of serotonin level manipulations on performance could be demonstrated, high serotonin levels appear to inhibit athletes' ability and motivation to perform an end sprint during exercise (Roelands et al., 2009). ...
Endurance sports are booming, with sports passionates of varying skills and expertise battering city streets and back roads on their weekly or daily exercise rounds. The investments required for performing in endurance exercise are nevertheless considerable, and passion for their sport might explain the efforts endurance athletes are willing to make. Passion may be defined as a strong motivational force and as such might be related to the neurophysiological basis underlying the drive to exercise.
A complex relationship between the brain and other systems is responsible for athletes’ exercise behaviour and thus performance in sports. We anticipate important consequences of athletes’ short term choices, for example concerning risk taking actions, on long term outcomes such as injuries, overtraining and burnout. We propose to consider athletes’ type of passion, in combination with neurophysiological parameters, as an explanatory factor in understanding the apparent disparity in the regulation of exercise intensity during endurance sports. Previous research has demonstrated that athletes can be passionate towards their sport in either a harmonious or an obsessive way. Although both lead to considerable investments and therefore often to successful performances, obsessive passion may affect athlete well-being and performance on the long run, due to the corresponding inflexible exercise behaviour.
In this perspective we will thus examine the influence of passion in sport on athletes’ short term and long term decision-making and exercise behavior, in particular related to the regulation of exercise intensity, and discuss the expected long term effects of both types of passion for sport.
... Other investigators have examined the possibility of hyperthermia-mediated altered brain neurotransmitter concentrations might contribute to fatigue during prolonged exercise (118,237,238,240,314). It has long been appreciated that different monoamines can alter thermoregulation (78,79,119) and changes in brain monoamine concentrations and/or ratios (e.g., serotonin, dopamine, and noradrenalin) might contribute to and/or mediate the premature fatigue during exercise-heat stress (172,241). ...
... As illustrated in Figure 1A, ambient temperature as a stand-alone factor is a poor predictor of the integrated environmental heat stress and apparently 2 of the prevailing heat stress indices,WBGT and UTCI (see Fig. 1C and D), also fail to predict the impact of environmental heat stress on TT performance. However, in studies where wind speed, humidity and radiation are controlled (remain constant across trials), [33][34][35][36][37][38] performance and the physiological responses are directly influenced by elevated air temperature, as it will limit dry heat loss and either 1) restrict the upper limit for heat dissipation thereby restricting the exercise intensity that may be endured due to constrained ability to maintain heat balance (i.e. storage and elevated body temperature become the limiting factors for the metabolic heat production that the athlete in the given temperature setting may sustain) or 2) it will elevate the skin temperature thereby superimposing a cardiovascular restrain on the ability to support the increased need for skin perfusion and maintenance of stroke volume and arterial oxygen delivery to the exercising muscles (for a detailed discussion of fatigue mechanisms and the impact of hyperthermia-induced cardiovascular versus central nervous temperature changes, please see ref. 39). ...
In this review we examine how self-paced performance is affected by environmental heat stress factors during cycling time trial performance as well as considering the effects of exercise mode and heat acclimatization. Mean power output during prolonged cycling time trials in the heat (≥30°C) was on average reduced by 15% in the 14 studies that fulfilled the inclusion criteria. Ambient temperature per se was a poor predictor of the integrated environmental heat stress and 2 of the prevailing heat stress indices (WBGT and UTCI) failed to predict the environmental influence on performance. The weighing of wind speed appears to be too low for predicting the effect for cycling in trained acclimatized subjects, where performance may be maintained in outdoor time trials at ambient temperatures as high as 36°C (36°C UTCI; 28°C WBGT). Power output during indoor trials may also be maintained with temperatures up to at least 27°C when humidity is modest and wind speed matches the movement speed generated during outdoor cycling, whereas marked reductions are observed when air movement is minimal. For running, representing an exercise mode with lower movement speed and higher heat production for a given metabolic rate, it appears that endurance is affected even at much lower ambient temperatures. On this basis we conclude that environmental heat stress impacts self-paced endurance performance. However, the effect is markedly modified by acclimatization status and exercise mode, as the wind generated by the exercise (movement speed) or the environment (natural or fan air movement) exerts a strong influence.
... Pharmacological manipulation of serotonin has generated mixed findings. Studies have reported modified endurance performance in rodents 8,9 and humans 10,11 , while others report no influence [12][13][14][15] . ...
Strenuous exercise can result in an inability of the central nervous system to drive skeletal muscle effectively, a phenomenon known as central fatigue. The impact of central fatigue on the oculomotor system is currently unexplored. Fatigue that originates in the central nervous system may be related to perturbations in the synthesis and metabolism of several neurotransmitters. In this study we examine central fatigue in the oculomotor system after prolonged exercise. The involvement of central neurotransmission was explored by administering caffeine during exercise. Within a double-blind, randomized, repeated measures, crossover design, 11 cyclists consumed a placebo or caffeine solution during 180 min of stationary cycling. Saccadic eye movements were measured using infra-red oculography. Exercise decreased saccade velocity by 8% (placebo trial). This effect was reversed by caffeine, whereby velocity was increased by 11% after exercise. A non-oculomotor perceptual task (global motion processing) was unaffected by exercise. The human oculomotor system is impaired by strenuous exercise of the locomotor system. Caffeine exerts a protective effect on oculomotor control, which could be related to up-regulated central neurotransmission. In addition, cortical processes supporting global motion perception appear to be robust to fatigue.
... When the 5-HT reuptake inhibitor citalopram was used to increase the brain content of 5-HT (78), no significant changes in endurance performance were detected. Also other studies (88,89), were not able to influence performance and therefore fatigue during exercise in a hot environment. ...
During exercise, there is a progressive reduction in the ability to produce muscle forces. Processes within the nervous system, as well as within the muscles contribute to this fatigue. In addition to impaired function of the motor system, sensations associated with fatigue, and impairment of homeostasis can contribute to impairment of performance during exercise. This review discusses some of the neural changes that accompany exercise and the development of fatigue. The role of brain monoaminergic neurotransmitter systems in whole-body endurance performance is discussed, particularly with regard to exercise in hot environments. Next, fatigue-related alterations in the neuromuscular pathway are discussed in terms of changes in motor unit firing, motoneuron excitability and motor cortical excitability. These changes have mostly been investigated during single-limb isometric contractions. Finally, the small-diameter muscle afferents that increase firing with exercise and fatigue are discussed. These afferents have roles in cardiovascular and respiratory responses to exercise, and in impairment of exercise performance through interaction with the motor pathway, as well as providing sensations of muscle discomfort. Thus, changes at all levels of the nervous system including the brain, spinal cord, motor output, sensory input and autonomic function occur during exercise and fatigue. The mix of influences and the importance of their contribution varies with the type of exercise being performed.
... For instance, treatment with a dopamine re-uptake inhibitor or serotonin antagonists has been shown to improve endurance performance in humans and rodents, respectively [58,59]. However, the role of serotonin in central fatigue mechanisms is less clear in humans, as serotonin re-uptake inhibition has been shown to have no influence on endurance performance [60]. Nevertheless, Mundel et al. [61,62] found that facial cooling significantly reduced blood prolactin concentration, which is stimulated by serotonin and inhibited by dopamine. ...
Intense training results in numerous physiological perturbations such as muscle damage, hyperthermia, dehydration and glycogen depletion. Insufficient/untimely restoration of these physiological alterations might result in sub-optimal performance during subsequent training sessions, while chronic imbalance between training stress and recovery might lead to overreaching or overtraining syndrome. The use of post-exercise cold water immersion (CWI) is gaining considerable popularity among athletes to minimize fatigue and accelerate post-exercise recovery. CWI, through its primary ability to decrease tissue temperature and blood flow, is purported to facilitate recovery by ameliorating hyperthermia and subsequent alterations to the central nervous system (CNS), reducing cardiovascular strain, removing accumulated muscle metabolic by-products, attenuating exercise-induced muscle damage (EIMD) and improving autonomic nervous system function. The current review aims to provide a comprehensive and detailed examination of the mechanisms underpinning acute and longer term recovery of exercise performance following post-exercise CWI. Understanding the mechanisms will aid practitioners in the application and optimisation of CWI strategies to suit specific recovery needs and consequently improve athletic performance. Much of the literature indicates that the dominant mechanism by which CWI facilitates short term recovery is via ameliorating hyperthermia and consequently CNS mediated fatigue and by reducing cardiovascular strain. In contrast, there is limited evidence to support that CWI might improve acute recovery by facilitating the removal of muscle metabolites. CWI has been shown to augment parasympathetic reactivation following exercise. While CWI-mediated parasympathetic reactivation seems detrimental to high-intensity exercise performance when performed shortly after, it has been shown to be associated with improved longer term physiological recovery and day to day training performances. The efficacy of CWI for attenuating the secondary effects of EIMD seems dependent on the mode of exercise utilised. For instance, CWI application seems to demonstrate limited recovery benefits when EIMD was induced by single-joint eccentrically biased contractions. In contrast, CWI seems more effective in ameliorating effects of EIMD induced by whole body prolonged endurance/intermittent based exercise modalities.
... Although pacing and/or overall performance may be altered when neurotransmitters are manipulated, typically no differences in perceived exertion or thermal stress are observed when compared with placebo trials [64][65][66][67]. It has been proposed that participants continuously modify their pace in order to match the momentary perceived exertion with the expected level of exertion at a given point during an exercise task [11]. ...
Ratings of perceived exertion (RPE) and effort are considered extremely important in the regulation of intensity during self-paced physical activity. While effort and exertion are slightly different constructs, these terms are often used interchangeably within the literature. The development of perceptions of both effort and exertion is a complicated process involving numerous neural processes occurring in various regions within the brain. It is widely accepted that perceptions of effort are highly dependent on efferent copies of central drive which are sent from motor to sensory regions of the brain. Additionally, it has been suggested that perceptions of effort and exertion are integrated based on the balance between corollary discharge and actual afferent feedback; however, the involvement of peripheral afferent sensory feedback in the development of such perceptions has been debated. As such, this review examines the possible difference between effort and exertion, and the implications of such differences in understanding the role of such perceptions in the regulation of pace during exercise.
... Other investigators have examined the possibility of hyperthermia-mediated altered brain neurotransmitter concentrations might contribute to fatigue during prolonged exercise (118,237,238,240,314). It has long been appreciated that different monoamines can alter thermoregulation (78,79,119) and changes in brain monoamine concentrations and/or ratios (e.g., serotonin, dopamine, and noradrenalin) might contribute to and/or mediate the premature fatigue during exercise-heat stress (172,241). ...
This article presents a historical overview and an up-to-date review of hyperthermia-induced fatigue during exercise in the heat. Exercise in the heat is associated with a thermoregulatory burden which mediates cardiovascular challenges and influence the cerebral function, increase the pulmonary ventilation, and alter muscle metabolism; which all potentially may contribute to fatigue and impair the ability to sustain power output during aerobic exercise. For maximal intensity exercise, the performance impairment is clearly influenced by cardiovascular limitations to simultaneously support thermoregulation and oxygen delivery to the active skeletal muscle. In contrast, during submaximal intensity exercise at a fixed intensity, muscle blood flow and oxygen consumption remain unchanged and the potential influence from cardiovascular stressing and/or high skin temperature is not related to decreased oxygen delivery to the skeletal muscles. Regardless, performance is markedly deteriorated and exercise-induced hyperthermia is associated with central fatigue as indicated by impaired ability to sustain maximal muscle activation during sustained contractions. The central fatigue appears to be influenced by neurotransmitter activity of the dopaminergic system, but inhibitory signals from thermoreceptors arising secondary to the elevated core, muscle and skin temperatures and augmented afferent feedback from the increased ventilation and the cardiovascular stressing (perhaps baroreceptor sensing of blood pressure stability) and metabolic alterations within the skeletal muscles are likely all factors of importance for afferent feedback to mediate hyperthermia-induced fatigue during submaximal intensity exercise. Taking all the potential factors into account, we propose an integrative model that may help understanding the interplay among factors, but also acknowledging that the influence from a given factor depends on the exercise hyperthermia situation.
... Indeed, cardiovascular limitations induced by adjustments in thermoregulation can significantly influence the maintenance of a given absolute intensity or pace, as was stated by Périard. Evidence from studies in our laboratory [5][6][7] showed that fixed-intensity exercise (60 min at 55 % of the maximal power output) resulted in significantly higher heart rates in hot conditions (30°C) when compared with normal (18°C) ambient temperature. Unfortunately, we did not measure stroke volume, cardiac output, or blood flow as was done in the study by Périard et al. [4] and that would have provided interesting information. ...
... 117 Inhibition of norepinephrine uptake (i.e. a more pronounced noradrenergic effect) was shown to significantly increase the time elapsed before the establishment of a drop in exercise performances under normal-temperature environments and heat as well, although there is also evidence suggesting that catecholamines may not affect the income of the fatigue status. 118 Physical exercise has many effects on the CNS, much more than mood influence. Peripheral signals generated during and after an exercise session, such as IL-6 and IL-10, decrease endoplasmic reticulum stress markers at hypothalamic level, an effect related to the decrease in NF-kB activation, 119 similarly to that observed by intracellular HSP70 expression. ...
Integrative physiology studies have shown that immune system and central nervous system interplay very closely towards behavioural modulation. Since the 70-kDa heat shock proteins (HSP70s), whose heavy expression during exercise is well documented in the skeletal muscle and other tissues, is also extremely well conserved in nature during all evolutionary periods of species, it is conceivable that HSP70s might participate of physiologic responses such as fatigue induced by some types of physical exercise. In this way, increased circulating levels of extracellular HSP70 (eHSP70) could be envisaged as an immunomodulatory mechanism induced by exercise, besides other chemical messengers (e.g. cytokines) released during an exercise effort, that are able to binding a number of receptors in neural cells. Studies from this laboratory led us to believe that increased levels of eHSP70 in the plasma during exercise and the huge release of eHSP70 from lymphocytes during high-load exercise bouts may participate in the fatigue sensation, also acting as a danger signal from the immune system.
A rise in body core temperature and loss of body water via sweating are natural consequences of prolonged exercise in the heat. This review provides a comprehensive and integrative overview of how the human body responds to exercise under heat stress and the countermeasures that can be adopted to enhance aerobic performance under such environmental conditions. The fundamental concepts and physiological processes associated with thermoregulation and fluid balance are initially described, followed by a summary of methods to determine thermal strain and hydration status. An outline is provided on how exercise-heat stress disrupts these homeostatic processes, leading to hyperthermia, hypohydration, sodium disturbances and in some cases exertional heat illness. The impact of heat stress on human performance is also examined, including the underlying physiological mechanisms that mediate the impairment of exercise performance. Similarly, the influence of hydration status on performance in the heat and how systemic and peripheral hemodynamic adjustments contribute to fatigue development is elucidated. This review also discusses strategies to mitigate the effects of hyperthermia and hypohydration on exercise performance in the heat, by examining the benefits of heat acclimation, cooling strategies and hyperhydration. Finally, contemporary controversies are summarized and future research directions provided.
Key points:
During maximal effort contractions, intense serotonin release via the raphe-spinal pathway spills over from the somato-dendritic compartment to activate inhibitory 5-HT1A receptors on the axon initial segment of motoneurons to reduce motoneuronal output. We investigated whether the same mechanism of central fatigue is present for low-intensity contractions, whereby weak serotonergic drive over an extended period may cause accumulation of serotonin and exacerbate central fatigue. Enhanced availability of serotonin did not directly influence motor pathways or motor performance during prolonged submaximal contraction. However, perceptions of muscle fatigue were greater, and the fatigue-induced lengthening of the silent period elicited via motor cortical stimulation was reduced with enhanced availability of serotonin. We propose that sustained low-intensity serotonergic neurotransmission influences supraspinal processes associated with fatigue, without directly influencing the output of the motor system during submaximal exercise.
Abstract:
Enhanced availability of serotonin (5-HT) exacerbates central fatigue that occurs during maximal effort contractions. However, it is unknown if 5-HT release contributes to central fatigue during prolonged submaximal contractions. Hence, we assessed the effect that enhanced availability of 5-HT has on sustained low-intensity fatiguing contractions. Fifteen individuals (22.3 ± 2.1 yr) ingested the 5-HT reuptake inhibitor paroxetine in a human, double-blinded, placebo-controlled, repeated-measures design. Participants performed a low-intensity isometric elbow flexion for 30 min (15% of maximal voluntary contraction, MVC). Throughout the protocol, brief MVCs were performed and muscle responses to transcranial magnetic stimulation (TMS) of the motor cortex, electrical stimulation of the brachial plexus, and motor point stimulation of the biceps were obtained. Ratings of perceived fatigue were also acquired. Paroxetine did not influence torque or voluntary activation during brief MVCs performed throughout the low-intensity contraction. However, paroxetine increased the perception of fatigue throughout the contraction (P = 0.005), and shortened the biceps silent period elicited via TMS during sustained submaximal contraction (P = 0.003) and brief MVCs (P = 0.011). Overall, it appears that prolonged low-intensity contractions does not cause intense 5-HT release onto motoneurons, and therefore, 5-HT does not activate inhibitory extra-synaptic 5-HT1A receptors of motoneurons to reduce their output. Although motor performance was unaffected by paroxetine, perceived fatigue was greater and intracortical inhibitory activity was reduced following the enhancement of endogenous concentrations of 5-HT during sustained submaximal contraction. Thus, 5-HT affects supraspinal processes during low-intensity contractions without directly altering motor pathways projecting to the muscle. This article is protected by copyright. All rights reserved.
Key points:
Animal preparations have revealed that moderate synaptic release of serotonin (5-HT) onto motoneurones enhances motor activity via activation of 5-HT2 receptors, whereas intense release of 5-HT causes spillover of 5-HT to extrasynaptic 5-HT1A receptors on the axon initial segment to reduce motoneurone activity. We explored if increasing extracellular concentrations of endogenously released 5-HT (via the SSRI paroxetine) influences the ability to unfatigued and fatigued maximal voluntary contractions in humans. Following the ingestion of paroxetine, voluntary muscle activation and torque generation increased during brief unfatigued maximal contractions. In contrast, the ability to generate maximal torque with increased 5-HT availability was compromised under fatigued conditions, which was consistent with paroxetine-induced reductions motoneurone excitability and voluntary muscle activation. This is the first in vivo human study to provide evidence that 5-HT released onto the motoneurones could play a role in central fatigue.
Abstract:
Brief stimulation of the raphe-spinal pathway in the turtle spinal cord releases serotonin (5-HT) onto motoneurones to enhance excitability. However, intense release of 5-HT via prolonged stimulation results in 5-HT spillover to the motoneurone axon initial segment to activate inhibitory 5-HT1A receptors, thus providing a potential spinal mechanism for exercise-induced central fatigue. We examined how increased extracellular concentrations of 5-HT affect the ability to perform brief, as well as sustained, maximal voluntary contractions (MVC) in humans. Paroxetine was used to enhance 5-HT concentrations by reuptake inhibition, and three studies were performed. Study 1 (n = 14) revealed that 5-HT reuptake inhibition caused ∼4% increase in elbow flexion MVC. However, when maximal contractions were sustained, time-to-task failure was reduced and self-perceived fatigue was higher with enhanced availability of 5-HT. Study 2 (n = 11) used twitch interpolation to reveal that 5-HT-based changes in motor performance had a neural basis. Enhanced 5-HT availability increased voluntary activation for the unfatigued biceps brachii and decreased voluntary activation of the biceps brachii by 2-5% following repeated maximal elbow flexions. The final study (n = 8) investigated whether altered motoneurone excitability may contribute to 5-HT changes in voluntary activation. F-waves of the abductor digiti minimi (ADM) were unaffected by paroxetine for unfatigued muscle and marginally affected following a brief 2-s MVC. However, F-wave area and persistence were significantly decreased following a prolonged 60-s MVC of the ADM. Overall, high serotonergic drive provides a spinal mechanism by which higher concentrations of 5-HT may contribute to central fatigue. This article is protected by copyright. All rights reserved.
The achievement of optimal performance during exercise is not a new area of interest among athletes, trainers, and coaches. Many tend to employ external performance enhancing devices or substances, such as improved clothing and footwear, nutritional beverages and high caloric (i.e., energy) shakes. However, those that solely rely on such external mechanisms to improve performance may still be limiting the potential of their athletes to achieve the absolute upper limits of a specific exercise endeavor. Regardless of the type of clothing, footwear, or ergogenic beverage, the athlete’s psychological and/or physiological capacities to attain and maintain maximal loads provides the greatest contribution to reach the upper limits of exercise performance. Information gained from these interrelated psychophysiological mechanisms, known collectively as teleoanticipation, incorporate memory from previously completed exercise along with both centrally generated efferent signals and peripheral afferent signals during exercise in order to minimize fatigue and obtain optimal performance. The assessment of an individual’s just noticeable difference (JND) in perceived exertion may assist in providing appropriate feedback during exercise intensity self-regulation to improve pacing strategy. The perceived exertion JND is a measure of an individual’s perceptual acuity, i.e., the smallest change in exercise intensity (expressed as VO2 or PO) that elicits a noticeable change in perceived exertion. The perceived exertion JND can be applied to the improvement and refinement of teleoanticipation to attain optimal exercise performance. The primary purpose of this laboratory experiment is to examine the use of the perceived exertion JND in a traditional RPE-based exercise prescription. Using the JND as identified in an estimation–production paradigm can in turn provide feedback during the production protocol regarding the accuracy of intensity self-regulation according to a target RPE.
Neurotransmitters in the brain, especially monoamines, are modulated by exercise. Interplay between exercise and monoamines, was initially explained by the “central fatigue hypothesis,” which increased brain serotonin release have been attributed to the onset of fatigue during prolonged exercise. However, because of the complexity of brain functions, it is unlikely that a single neurotransmitter system is responsible for central fatigue. Several other mechanisms are involved, and the evidence supports the role of brain dopamine (DA) and noradrenaline (NA). In recent decennia, Roelands and Meeusen (2010) suggested that brain serotonin, DA, and NA might play an important role in thermoregulation and hyperthermia-induced fatigue, specifically when exercising in the heat. It opened a window of opportunity for several research groups that tried to manipulate performance, and to delay or induce fatigue by different pharmacological interventions that affected brain monoamine release, at normal and high ambient temperatures.
Strenuous exercise can result in an inability of the central nervous system to drive skeletal muscle effectively, a phenomenon known as central fatigue. The impact of central fatigue on the oculomotor system is currently unexplored. Fatigue that originates in the central nervous system may be related to perturbations in the synthesis and metabolism of several neurotransmitters. In this study we examine central fatigue in the oculomotor system after prolonged exercise. The involvement of central neurotransmission was explored by administering caffeine during exercise. Within a double-blind, randomized, repeated measures, crossover design, 11 cyclists consumed a placebo or caffeine solution during 180 min of stationary cycling. Saccadic eye movements were measured using infra-red oculography. Exercise decreased saccade velocity by 8% (placebo trial). This effect was reversed by caffeine, whereby velocity was increased by 11% after exercise. A non-oculomotor perceptual task (global motion processing) was unaffected by exercise. The human oculomotor system is impaired by strenuous exercise of the locomotor system. Caffeine exerts a protective effect on oculomotor control, which could be related to up-regulated central neurotransmission. In addition, cortical processes supporting global motion perception appear to be robust to fatigue.
The human capacity to perform prolonged exercise is impaired in hot environments. To address this issue, a number of studies have investigated behavioral aspects of thermoregulation that are recognized as important factors in determining performance. In this review, we evaluated and interpreted the available knowledge regarding the voluntary control of exercise work rate in hot environments. Our analysis indicated that: (a) Voluntary reductions in exercise work rate in uncompensable heat aid thermoregulation and are, therefore, thermoregulatory behaviors. (b) Unlike thermal behavior during rest, the role of thermal comfort as the ultimate mediator of thermal behavior during exercise in the heat remains uncertain. By contrast, the rating of perceived exertion appears to be the key perceptual controller under such conditions, with thermal perception playing a more modulatory role. (c) Prior to increases in core temperature (when only skin temperature is elevated), reductions in self-selected exercise work rate in the heat are likely mediated by thermal perception (thermal comfort and sensation) and its influence on the rating of perceived exertion. (d) However, when both core and skin temperatures are elevated, factors associated with cardiovascular strain likely dictate the rate of perceived exertion response, thereby mediating such voluntary reductions in exercise work rate.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The literature survey 2009 is based on 743 papers found in the databases MEDLINE and EMBASE with the keywords “thermography” or “thermometry” or “thermotherapy” or ‘skin temperature’ or ‘core temperature’ and restricted to “humans” and “included in the databases between 01-01 and 31-12 2009”. 43 percent of papers of this review are originated from Europe and 91.5 percent of all papers are written in English. 266 controlled studies using some kind of temperature measurement were reported. Physiology, surgery, dermatology, neurology, clinical and experimental pharmacology were the predominant fields of applications of temperature measurement in medicine. Therapeutic hyperthermia and hypothermia treatment was the topic of many papers. Fever attracted also a high publication interest. Only some papers were related to intravascular temperature measurement, Raynaud´s phenomenon or breast thermography.
Aim: To determine the effect of prolonged intensive cycling and post-exercise recovery in the heat on brain sources of altered brain oscillations. Methods: After a max test and familiarization trial, 9 trained male subjects (23 ± 3 yrs; maximal oxygen uptake = 62.1 ± 5.3 mL•min(-1)•kg(-1)) performed 3 experimental trials in the heat (30°C; RH 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1h. The first was a 60min constant load trial, followed by a 30min simulated time trial (TT1). The second comprised a 12min simulated time trial (TT2). After TT1 active recovery (AR), passive rest (PR) or cold water immersion (CWI) was applied for 15min. EEG was measured at baseline and during post-exercise recovery. sLORETA was applied to accurately pinpoint and localize altered electrical neuronal activity. Results: After CWI, PR and AR subjects completed TT2 in 761 ± 42s, 791 ± 76s and 794 ± 62s respectively. A prolonged intensive cycling performance in the heat decreased β activity along the whole brain. Post-exercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in BA 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Discussion: Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Post-exercise CWI increased β3 activity at Brodmann Areas 13 and 40, brain areas involved in somatosensory information processing.
Purpose:
To determine the effect of active recovery (AR), passive rest (PR), and cold-water immersion (CWI) after 90 min of intensive cycling on a subsequent 12-min time trial (TT2) and the applied pacing strategy in TT2.
Methods:
After a maximal test and familiarization trial, 9 trained male subjects (age 22 ± 3 y, VO2max 62.1 ± 5.3 mL · min-1 · kg-1) performed 3 experimental trials in the heat (30°C). Each trial consisted of 2 exercise tasks separated by 1 h. The first was a 60-min constant-load trial at 55% of the maximal power output followed by a 30-min time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, AR, PR, or CWI was applied for 15 min.
Results:
No significant TT2 performance differences were observed, but a 1-sample t test (within each condition) revealed different pacing strategies during TT2. CWI resulted in an even pacing strategy, while AR and PR resulted in a gradual decline of power output after the onset of TT2 (P ≤ .046). During recovery, AR and CWI showed a trend toward faster blood lactate ([BLa]) removal, but during TT2 significantly higher [BLa] was only observed after CWI compared with PR (P = .011).
Conclusion:
The pacing strategy during subsequent cycling performance in the heat is influenced by the application of different postexercise recovery interventions. Although power was not significantly altered between groups, CWI enabled a differently shaped power profile, likely due to decreased thermal strain.
Fatigue during prolonged exercise is often described as an acute impairment of exercise performance that leads to an inability to produce or maintain a desired power output. In the past few decades, interest in how athletes experience fatigue during competition has grown enormously. Research has evolved from a dominant focus on peripheral causes of fatigue towards a complex interplay between peripheral and central limitations of performance. Apparently, both feedforward and feedback mechanisms, based on the principle of teleoanticipation, regulate power output (e.g. speed) during a performance. This concept is called ‘pacing’ and represents the use of energetic resources during exercise, in a way such that all energy stores are used before finishing a race, but not so far from the end of a race that a meaningful slowdown can occur.
It is believed that the pacing selected by athletes is largely dependent on the anticipated exercise duration and on the presence of an experientially developed performance template. Most studies investigating pacing during prolonged exercise in ambient temperatures, have observed a fast start, followed by an even pace strategy in the middle of the event with an end sprint in the final minutes of the race. A reduction in pace observed at commencement of the event is often more evident during exercise in hot environmental conditions. Further, reductions in power output and muscle activation occur before critical core temperatures are reached, indicating that subjects can anticipate the exercise intensity and heat stress they will be exposed to, resulting in a tactical adjustment of the power output. Recent research has shown that not only climatic stress but also pharmacological manipulation of the central nervous system has the ability to cause changes in endurance performance. Subjects seem to adapt their strategy specifically in the early phases of an exercise task. In high-ambient temperatures, dopaminergic manipulations clearly improve performance. The distribution of the power output reveals that after dopamine reuptake inhibition, subjects are able to maintain a higher power output compared with placebo. Manipulations of serotonin and, especially, noradrenaline, have the opposite effect and force subjects to decrease power output early in the time trial. Interestingly, after manipulation of brain serotonin, subjects are often unable to perform an end sprint, indicating an absence of a reserve capacity or motivation to increase power output. Taken together, it appears that many factors, such as ambient conditions and manipulation of brain neurotransmitters, have the potential to influence power output during exercise, and might thus be involved as regulatory mechanisms in the complex skill of pacing.
Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p-CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p-CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 μM) and underwent a submaximal exercise test until fatigue. Icv TRP-treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p-CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p-CPA administration accelerated cutaneous heat dissipation when compared with saline-pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p-CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.
We examined the effect of heat acclimation (HA) on endurance capacity and blood prolactin (PRL) response to moderate intensity exercise in the heat in young male subjects (n = 21). Three exercise tests (ET) were completed on a treadmill: H1 (walk at 60% VO2peak until exhaustion at 42°C), N (walk at 22°C; duration equal to H1) and H2 (walk until exhaustion at 42°C after a 10-day HA program). Heart rate (HR), skin (T
sk) and core (T
c) temperatures and body heat storage (HS) were measured. Blood samples were taken immediately before, during and immediately after each ET. HA resulted in lower HR, T
sk, T
c and HS rate (P < 0.05) during ET, whereas endurance capacity increased from 88.6 ± 27.5 min in H1 to 162.0 ± 47.8 min in H2 (P < 0.001). Blood PRL concentration was lower (P < 0.05) during exercise in H2 compared to H1 but the peak PRL level observed at the time of exhaustion did not differ in the two trials. Blood PRL concentration at 60 min of exercise in H1 correlated with time to exhaustion in H1 (r = –0.497, P = 0.020) and H2 (r = –0.528, P = 0.014). In conclusion, HA slows down the increase in blood PRL concentration but does not reduce the peak PRL level occurring at the end of exhausting endurance exercise in the heat. Blood PRL response to exercise in the heat in non-heat-acclimated subjects is associated with their endurance capacity in the heat in a heat-acclimated state.
Fatigue is a complex phenomenon that can be evoked by peripheral and central factors. Although it is obvious that fatigue has peripheral causes such as glycogen depletion and cardiovascular strain, recent literature also focuses on the central origin of fatigue. It is clear that different brain neurotransmitters--such as serotonin, dopamine and noradrenaline--are implicated in the occurrence of fatigue, but manipulation of these neurotransmitters produced no conclusive results on performance in normal ambient temperature. Exercise in the heat not only adds an extra challenge to the cardiorespiratory system, but also to the brain. This provides a useful tool to investigate the association between exercise-induced hyperthermia and central fatigue. This review focuses on the effects of pharmacological manipulations on performance and thermoregulation in different ambient temperatures. Dopaminergic reuptake inhibition appears to counteract hyperthermia-induced fatigue in 30 °C, while noradrenergic neurotransmission shows negative effects on performance in both normal and high temperature, and serotonergic manipulations did not lead to significant changes in performance. It is, however, unlikely that one neurotransmitter system is responsible for the delay or onset of fatigue. Further research is required to determine the exact mechanisms of fatigue in different environmental conditions.
The scientific evidence is reviewed for the involvement of the brain monoamines serotonin, dopamine and noradrenaline (norepinephrine) in the onset of fatigue, in both normal and high ambient temperatures. The main focus is the pharmacological manipulations used to explore the central fatigue hypothesis. The original central fatigue hypothesis emphasizes that an exercise-induced increase in serotonin is responsible for the development of fatigue. However, several pharmacological studies attempted and failed to alter exercise capacity through changes in serotonergic neurotransmission in humans, indicating that the role of serotonin is often overrated. Recent studies, investigating the inhibition of the reuptake of both dopamine and noradrenaline, were capable of detecting changes in performance, specifically when ambient temperature was high. Dopamine and noradrenaline are prominent in innervated areas of the hypothalamus, therefore changes in the catecholaminergic concentrations may also be expected to be involved with the regulation of body core temperature during exercise in the heat. Evidence from different studies suggests that it is very unlikely that one neurotransmitter system is responsible for the appearance of central fatigue. The exact mechanism of fatigue is not known; presumably a complex interplay between both peripheral and central factors induces fatigue. Central fatigue will be determined by the collaboration of the different neurotransmitter systems, with the most important role possibly being for the catecholamines dopamine and noradrenaline.
Effects of paroxetine (10 mg/kg PO, twice daily, 14 days) on 5-HT receptor subpopulations in the brain were evaluated pharmacologically, electrophysiologically and biochemically in male Wistar rats. Imipramine was used for comparison. Repeated paroxetine antagonized the 8-OH-DPAT-induced behavioural syndrome (a 5-HT1A effect); imipramine showed similar, yet weaker, activity. The 5-HT-or 8-OH-DPAT-induced inhibition of population spikes in hippocampal slices was increased by both those repeated antidepressants. Repeated (or acute) paroxetine decreased the density of and increased the affinity for 5-HT1A receptors ([3H]-8-OH-DPAT used as ligand) in the hippocampus, while imipramine induced opposite effects. m-Chlorophenyl piperazine (m-CPP)-evoked exploratory hypoactivity, a 5-HT2C effect, was reduced by repeated paroxetine, but not by imipramine. Either of the antidepressants given repeatedly antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head twitches (a 5-HT2A effect) were inhibited by repeated paroxetine or imipramine. Either antidepressant given repeatedly decreased the density of 5-HT2A receptors ([3H]-ketanserin as a ligand) in the brain cortex, but did not change their affinity. The present results indicate that paroxetine given repeatedly induces secondary changes in 5-HT2 receptors, which lead to reduction of the 5-HT2 neurotransmission (reduced responsiveness of 5-HT2 postsynaptic receptors). The consequences of the secondary changes in 5-HT1A receptors, found here still await clarification.
Changes in plasma hormonal concentrations during exercise have been ascribed to the type, duration, and intensity of exercise, physical fitness of subjects, oxygen availability and debt, and acid-base balance. However, relatively few studies have examined the possible role of exercise-induced hyperthermia. This paper reviews previous studies on this subject and describes a series of experiments carried out in our laboratories to define the role of changes in body temperature in the release of hormones during exercise. In a first series of experiments, we studied the relationship between thermoregulatory and growth hormone responses to severe exercise at 23 degrees C for 2 h in fit euhydrated subjects, controlling the core temperature increase to a maximum of 40 degrees C by varying wind speed. Exponential relationships were found between increases in core temperature and plasma growth hormone, prolactin, and catecholamines during exercise, suggesting the existence of a thermal threshold for stimulation of hormonal release during exercise. The effect of endurance exercise with and without a thermal clamp (immersion in cold and warm water) on hormonal and leukocyte responses was examined. Again, a significant exponential relationship was found between increases in core temperature and hormonal responses. Thermal clamping significantly diminished the hormonal and the leukocytic responses to exercise, suggesting that an exercise-induced thermal threshold of approximately 38 degrees C exists where hormonal responses are observed. Therefore, core temperature increases may be integrated in the controlling system of hormonal and leukocytic responses to exercise.
This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 +/- 0.1 degrees C (mean +/- SE) in the control trial, whereas it increased to 39.7 +/- 0.2 degrees C in the hyperthermic trial, with a concomitant increase in perceived exertion (P < 0.05). At rest, the brain had a small release of tryptophan (arteriovenous difference of -1.2 +/- 0.3 micromol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 +/- 0.3 (P < 0.05), whereas it returned to the baseline level of approximately 6 within 5 min after the control trial. The lowering of O2/CHO was established by an increased arteriovenous glucose difference (1.1 +/- 0.1 mmol/l during recovery from hyperthermia vs. 0.7 +/- 0.1 mmol/l in control; P < 0.05). The present findings indicate that the brain has an increased need for carbohydrates during recovery from strenuous exercise, whereas enhanced perception of effort as observed during exercise with hyperthermia was not related to alterations in the cerebral balances of dopamine or tryptophan.
Acute oral administration of selective serotonin re-uptake inhibitors (SSRIs) increases plasma cortisol by facilitating brain serotonin activity. Recently, salivary cortisol sampling has grown in popularity as a noninvasive means of assessing HPA axis activity. The aim of the present study was to find out whether acute oral administration of the SSRI, citalopram, increases salivary cortisol in healthy volunteers and whether the increase produced by an equivalent dose of its active isomer, escitalopram, is greater. A total of 15 healthy subjects were tested on three occasions receiving either oral citalopram (20 mg), escitalopram (10 mg), or placebo in a double-blind, randomized, crossover design. Salivary cortisol and plasma cortisol and prolactin were measured for 240 min after each treatment. Relative to placebo, both citalopram and escitalopram increased salivary and plasma cortisol levels with no evidence of consistent differences between them. Plasma prolactin concentration was not altered by either active treatment. Plasma and salivary cortisol responses after citalopram but not escitalopram correlated significantly. The present study does not support an enhanced effect of escitalopram on 5-HT-mediated neuroendocrine responses.
The original central fatigue hypothesis suggested that an exercise-induced increase in extracellular serotonin concentrations in several brain regions contributed to the development of fatigue during prolonged exercise. Serotonin has been linked to fatigue because of its well known effects on sleep, lethargy and drowsiness and loss of motivation. Several nutritional and pharmacological studies have attempted to manipulate central serotonergic activity during exercise, but this work has yet to provide robust evidence for a significant role of serotonin in the fatigue process. However, it is important to note that brain function is not determined by a single neurotransmitter system and the interaction between brain serotonin and dopamine during prolonged exercise has also been explored as having a regulative role in the development of fatigue. This revised central fatigue hypothesis suggests that an increase in central ratio of serotonin to dopamine is associated with feelings of tiredness and lethargy, accelerating the onset of fatigue, whereas a low ratio favours improved performance through the maintenance of motivation and arousal. Convincing evidence for a role of dopamine in the development of fatigue comes from work investigating the physiological responses to amphetamine use, but other strategies to manipulate central catecholamines have yet to influence exercise capacity during exercise in temperate conditions. Recent findings have, however, provided support for a significant role of dopamine and noradrenaline (norepinephrine) in performance during exercise in the heat. As serotonergic and catecholaminergic projections innervate areas of the hypothalamus, the thermoregulatory centre, a change in the activity of these neurons may be expected to contribute to the control of body temperature whilst at rest and during exercise. Fatigue during prolonged exercise clearly is influenced by a complex interaction between peripheral and central factors.
Combined inhibition of dopamine (DA)/norepinephrine (NE) reuptake improves exercise performance and increases core temperature in the heat. A recent study demonstrated that this effect may primarily be related to increased DA activity. NE reuptake inhibition (NERI), however, has received little attention in humans, certainly in the heat, where central fatigue appears to be a main factor influencing performance. Therefore the present study examines the effect of NERI (reboxetine) on exercise capacity, thermoregulation, and hormonal response in normal and high temperature. Nine healthy well-trained male cyclists participated in this study. Subjects ingested either placebo (Pla; 2 x 8 mg) or reboxetine (Rebox; 2 x 8 mg). Subjects exercised in temperate (18 degrees C) or warm (30 degrees C) conditions and cycled for 60 min at 55% W(max) immediately followed by a time trial (TT; Pla18/Rebox18; Pla30/Rebox30) to measure exercise performance. Acute NERI decreased power output and consequently exercise performance in temperate (P = 0.018) and warm (P = 0.007) conditions. Resting heart rate was significantly elevated by NERI (18 degrees C: P = 0.02; 30 degrees C: P = 0.018). In Rebox18, heart rate was significantly higher than in the Pla18, while in the heat no effect of the drug treatment was reported during exercise. In Rebox30, all hormone concentrations increased during exercise, except for growth hormone (GH), which was significantly lower during exercise. In Rebox18, prolactin (PRL) concentrations were significantly elevated; GH was significantly higher at rest, but significantly lower during exercise. In conclusion, manipulation of the NE system decreases performance and modifies hormone concentrations, thereby indicating a central NE effect of the drug. These findings confirm results from previous studies that predominantly increased DA activity is important in improving performance.
Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') causes persistent alterations to the serotonergic system of animals, evidence for long-term neurological effects of ecstasy/MDMA in humans remains equivocal. The current study assessed serotonin functioning of nine male and 11 female recreational ecstasy polydrug users by measuring neuroendocrine (prolactin, cortisol) responses to pharmacological challenge with the selective serotonin reuptake inhibitor citalopram, compared with nine male and five female cannabis polydrug users and 11 male and 11 female non-drug using controls. A single-blind, randomised, placebo-controlled design was used. Subjective responses, other substance use, mood, personality traits and demographic variables were measured to control for potentially confounding variables. There were no significant differences between ecstasy polydrug users, cannabis polydrug users and non-drug using controls in neuroendocrine or subjective responses to serotonergic challenge, and there were no sex by drug group interactions. There was no relationship between extent of ecstasy use and neuroendocrine functioning, alone or in combination with potential confounding variables. Subjective responses to the pharmacological challenge (nausea, tremor, dry mouth), novelty seeking and lifetime dose of alcohol were the only variables that contributed to one or more of the neuroendocrine outcome variables. These data do not support the premise that recreational ecstasy/MDMA use results in measurable impairment of serotonergic control of endocrine activity.
The hypothalamus, particularly the paraventricular nucleus (PVN), plays a central role in coordinating and regulating neuroendocrine function. Axons from cells originating in the PVN release corticotropin-releasing hormone (CRH) into the hypophysial portal vessels. CRH is then transported to the anterior pituitary gland, where it controls the release of corticotropin (adrenocorticotropic hormone, ACTH), leading to increased secretion of adrenal glucocorticoids (cortisol in humans, corticosterone in rats) (Swanson and Sawchenk 1983; Sawchenk Swanson 1985). Activation of other cells in the PVN increases prolactin release from the anterior lobe of the pituitary gland (Bagdy and Makara 1994, 1995; Bluet Pajot et al. 1995; Rittenhouse et al. 1993; Arey and Freeman 1992: Minamitani et al. 1987; Kiss et al. 1986). Cells in the PVN and supraoptic nucleus (SON) that synthesize oxytocin and vasopressin release these peptides into the circulation from their nerve terminals in the posterior (neural) lobe of the pituitary gland (Swanson and Sawchenko 1983). Finally, cells in the PVN are also important in the regulation of renin release from the kidneys (Rittenhouse et al. 1992b; Richardson Morton et al. 1989).
The original central fatigue hypothesis suggested that an exercise-induced increase in extracellular serotonin concentrations in several brain regions contributed to the development of fatigue during prolonged exercise. Serotonin has been linked to fatigue because of its well known effects on sleep, lethargy and drowsiness and loss of motivation. Several nutritional and pharmacological studies have attempted to manipulate central serotonergic activity during exercise, but this work has yet to provide robust evidence for a significant role of serotonin in the fatigue process. However, it is important to note that brain function is not determined by a single neurotransmitter system and the interaction between brain serotonin and dopamine during prolonged exercise has also been explored as having a regulative role in the development of fatigue. This revised central fatigue hypothesis suggests that an increase in central ratio of serotonin to dopamine is associated with feelings of tiredness and lethargy, accelerating the onset of fatigue, whereas a low ratio favours improved performance through the maintenance of motivation and arousal. Convincing evidence for a role of dopamine in the development of fatigue comes from work investigating the physiological responses to amphetamine use, but other strategies to manipulate central catecholamines have yet to influence exercise capacity during exercise in temperate conditions. Recent findings have, however, provided support for a significant role of dopamine and noradrenaline (norepinephrine) in performance during exercise in the heat. As serotonergic and catecholaminergic projections innervate areas of the hypothalamus, the thermoregulatory centre, a change in the activity of these neurons may be expected to contribute to the control of body temperature whilst at rest and during exercise. Fatigue during prolonged exercise clearly is influenced by a complex interaction between peripheral and central factors.
The combination of acute dopamine/noradrenaline reuptake inhibition (bupropion; BUP) and heat stress (30°C) significantly improves performance (9%). Furthermore the maintenance of a higher power output resulted in the attainment of significantly higher heart rates and rectal temperatures—above 40°C—in the BUP trial compared to the placebo trial. Since BUP is an aid to cease smoking that is taken for longer periods, question remains if similar performance and thermoregulatory effects are found following administration of BUP over several days (10 days). The purpose of the present study was to examine the effects of chronic BUP on exercise performance, thermoregulation and hormonal variables in the heat. Eight trained male cyclists participated in the study. Subjects completed two trials consisting of 60 min fixed intensity exercise (55% W
max) followed by a time trial (TT) in a double-blind randomized crossover design. Exercise was performed in 30°C. Subjects took either placebo (PLAC) or BUP (Zyban™) for 3 days (150 mg), followed by 300 mg for 7 days. Chronic BUP did not influence TT performance (BUP 40′42″ ± 4′18″; PLAC 41′36″ ± 5′12″), but significantly increased core temperature (P = 0.030). BUP significantly increased circulating growth hormone levels (PLAC: 9.8 ± 5.8 ng L−1; BUP: 13 ± 6.8 ng L−1; P < 0.008). Discussion/conclusion: Chronic BUP did not influence TT performance in 30°C and subjects did not reach core temperature values as high as observed during the acute BUP study. It seems that chronic administration results in an adaptation of central neurotransmitter homeostasis, resulting in a different response to the drug.
Male Wistar rats were housed in cages linked to running wheels and fed on a schedule designed to reduce their body weight by 20-30%. During this period of semistarvation, rats increased their daily running wheel activity (RWA) by up to 30 km/day. RWA could be kept at this level provided that body weight was kept constant. Different alpha-adrenergic agonists and antagonists were tested for their effects on RWA and it was found that RWA could be suppressed only by agonists that display high affinity for the alpha 2-receptor (clonidine and guanfacine). Neither antagonist had an effect on RWA. Clonidine's inhibiting effect on RWA was prevented by pretreatment with yohimbine, which also has high affinity for alpha 2-receptors. From these results, we conclude that semistarvation-induced hyperactivity can be blocked by alpha 2-agonists. In view of this result and those that were obtained in previous studies, a theoretical model for the development of semistarvation-induced hyperactivity will be presented.
Seven healthy subjects exercised to exhaustion on a bicycle ergometer at a power output corresponding to 70% of maximum oxygen uptake after administration of either a placebo or 20 mg of paroxetine, a serotonin re-uptake inhibitor. Exercise time after paroxetine (median 94 min; range 84-127 min) was less (P < 0.05) than after placebo (median 116 min; range 86-133 min). The metabolic and cardiorespiratory responses to exercise were the same in both trials. This result supports the suggestion that there is a central component to fatigue which is mediated by the activity of serotoninergic neurones.
The core temperature of male Wistar rats was measured after local application of 5-HT (10 micrograms) or 8-OH-DPAT (5 micrograms) into the dorsal (DR) or the median raphe (MR) nuclei. The core temperature was measured by a rectal thermistor probe, 20 and 60 min after the injection procedure started. The injected volume was 0.5 microliter and injections were made by means of 31G needles, at a rate of 0.33 microliter min-1. The raphe nuclei were approached at 30 degrees in order to avoid penetration of the cerebral aqueduct or to avoid the DR with injections aimed for the MR. The application of 5-HT or the 5-HT1A agonist 8-OH-DPAT into the DR produced a marked decrease in core temperature, whereas injections into the MR had no effect. These results demonstrate an important role for the DR in temperature regulation in the rat. The fact that the 5-HT1A agonist 8-OH-DPAT produced a decrease in core temperature, together with the observation that administration of the 5-HT1 antagonist (-)pindolol antagonized the 5-HT as well as the 8-OH-DPAT-induced decrease, indicates the involvement of DR 5-HT1A receptors in rat thermoregulation.
This study was performed to investigate the effects of exercise on the synthesis of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain of the trained rat. The consequences on the relationships between these two systems were also examined. The sum of the levels of free 3,4-dihydroxyphenyl acetic acid (DOPAC) plus homovanillic acid (HVA) was increased by running and remained elevated throughout the first hour of recovery. Regional studies indicated that the levels of DA were increased in the midbrain, hypothalamus and hippocampus. In these areas, DOPAC showed little variation whereas HVA was largely increased. Administration of pargyline confirmed this increase in the metabolism of DA in hypothalamus and midbrain during running. Food deprivation and administration of tryptophan clearly revealed that running, despite increasing levels of tryptophan and 5-hydroxyindoleacetic acid in brain, reduced the central control of synthesis of 5-HT by tryptophan, probably by inhibiting tryptophan hydroxylase. To examine if such an alteration was caused by the running-induced activation of metabolism of DA in brain, compounds known to affect the activity of DA were used. Administration of amphetamine potentiated the relative inhibition of synthesis of 5-HT induced by running, while alpha-methyl-p-tyrosine prevented this effect of exercise. Haloperidol did not produce any significant change. It is concluded that the control of the synthesis of 5-HT in brain by the availability of tryptophan is altered during exercise and that the increased central catecholaminergic activity participates in such an alteration.
1. Either electrical stimulation of midbrain raphe nuclei or administration of 5-hydroxytryptamine (5-HT; serotonin) into the preoptic anterior hypothalamus caused hypothermia in conscious rats at ambient temperatures (Ta) of both 8 degrees C and 22 degrees C. The hypothermia was due to decreased metabolic heat production at Ta = 8 degrees C, while at Ta = 22 degrees C the hypothermia was due to both decreased metabolism and increased heat loss (cutaneous vasodilatation). However, at Ta = 30 degrees C, electrical stimulation of midbrain raphe or intrahypothalamic injection of 5-HT caused an insignificant change in the thermoregulatory responses. There was no changes in respiratory evaporative heat loss in response to these treatments at various Ta's. 2. Direct administration of the serotonergic receptor antagonists such as cyproheptadine and methysergide into the preoptic anterior hypothalamus caused hyperthermia in conscious rats at Ta's of 8 degrees C, 22 degrees C and 30 degrees C. The hyperthermia was due to increased metabolism and cutaneous vasoconstriction. 3. The hypothermia induced by intrahypothalamic administration of 5-HT was antagonized by pretreatment with an intrahypothalamic dose of either cyproheptadine or methysergide in rats at Ta = 22 degrees C. 4. Inhibition of 5-HT neuronal activity with administration of 5-HT into the midbrain raphe regions also caused hyperthermia, increased metabolism and cutaneous vasoconstriction in rats at Ta's of 8 degrees C, 22 degrees C and 30 degrees C. 5. These observations tend to suggest that the functional activity of serotonergic receptors in the preoptic anterior hypothalamus mediates thermoregulatory responses in the rat. Activation of serotonergic receptors in the hypothalamus decreases heat production and/or increases heat loss, while inhibition of serotonergic receptors in the hypothalamus increases heat production and/or decreases heat loss in the rat.
There is a great demand for perceptual effort ratings in order to better understand man at work. Such ratings are important complements to behavioral and physiological measurements of physical performance and work capacity. This is true for both theoretical analysis and application in medicine, human factors, and sports. Perceptual estimates, obtained by psychophysical ratio-scaling methods, are valid when describing general perceptual variation, but category methods are more useful in several applied situations when differences between individuals are described. A presentation is made of ratio-scaling methods, category methods, especially the Borg Scale for ratings of perceived exertion, and a new method that combines the category method with ratio properties. Some of the advantages and disadvantages of the different methods are discussed in both theoretical-psychophysical and psychophysiological frames of reference.
1. Intrahypothalamic injection of either dopamine or 5-hydroxytryptamine (5-HT) in a dose volume of 1 microliters caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degree C. 2. Haloperidol (6.5 n-mole), a dopamine antagonist, prevented the hypothermic effect of dopamine (65 n-mole), but was ineffective against the response to either intrahypothalamic 5-HT (114 n-mole) or oxotremorine (6.0 n-mole). 3. Methysergide (14 n-mole) and cryproheptadine (17 n-mole) blocked the effect of both 5-HT and dopamine. However, these same doses failed to antagonise the effect of oxotremorine. 4. Rats placed on 0.65 m below a 250 W infra-red lamp responded to the imposed heat load vasodilation of tail skin blood vessels, as indicated by an increased tail skin temperature. 5. Rats tested 2 weeks after bilateral intrahypothalamic injection of 5,6-dihydroxytryptamine (42 n-mole in 2 microliters) showed a significant reduction in their tail skin temperature response and were less able to withstand the imposed heat load. 6. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the previously defined dopamine-sensitive site. 7. Pretreatment with 5,6-dihydroxytryptamine significantly reduced the 5-HT concentration in the dopamine sensitive site, but had no effect on the concentration of dopamine. This pretreatment blocked dopamine but not 5-HT-induced hypothermia. 8. The 5-hydroxyindoleacetic acid (5HIAA) concentration in the hypothalamus of the normal rat exposed to a heat load was found to be significantly elevated, whereas there was no change in the 5HIAA concentration in the cortex. 9. Slices of rat preoptic hypothalamus and hippocampus were incubated with [3H]5-HT (0.2-2 microM). These slices accumulated 5-HT with properties characteristic of a neuronal uptake process. 10. Perfusion with either dopamine (greater than 50 microM) or apomorphine (greater than 200 microM) enhanced the release of [3H]5-HT from the prelabelled hypothalamic slices, but failed to stimulate release from hippocampal slices. 11. The release of [3H]5-HT from preoptic slices by dopamine and apomorphine was antagonised by the dopamine antagonists haloperidol (2 microM) and (+) isomer of butaclamol (1 microM), the (-) isomer of butaclamol was inactive. 12. These results support the hypothesis of a dopamine-5HT link in the hypothalamic thermoregulatory pathways of the rat.
These studies examined the hypothalamic site and receptor subtype mediating the serotonergic (5-HT) control of PRL secretion in conscious male rats. Initially, we characterized the pharmacology of the 5-HT releaser and 5-HT agonists that increase PRL release. Subsequently, we performed lesion experiments to locate the 5-HT receptors involved in PRL secretion. p-Chloroamphetamine, a 5-HT releaser, is postulated to enter serotonergic nerve terminals through the 5-HT uptake mechanism, which can be inhibited by fluoxetine. p-Chloroamphetamine (8 mg/kg, ip) increased the plasma PRL concentration approximately 6-fold. The 5-HT uptake inhibitor fluoxetine almost completely prevented this increase, demonstrating that p-chloroamphetamine increases PRL release via a serotonergic mechanism. The 5-HT1C/5-HT2 agonist +(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl (ip) produced a strong (30-fold) dose-dependent elevation of plasma PRL, which was virtually eliminated by 0.1 mg/kg (sc) ritanserin, a 5-HT1C/5-HT2 antagonist. +(-)-1-(2,5-Dimethoxy-4-iodophenyl)2-aminopropane HCl injected intracerebroventricularly (icv) in doses below those that were peripherally effective also produced a significant (8-fold) increase in PRL secretion that was again attenuated by icv pretreatment with ritanserin (2 micrograms/kg). RU 24969 (5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]1H-indole) was reported to act as both a 5-HT releaser and a direct postsynaptic 5-HT agonist. To test whether RU 24969 releases 5-HT to increase PRL secretion, we depleted 5-HT stores with the 5-HT synthesis inhibitor p-chlorophenylalanine. The ability of RU 24969 (0.5, 1, 5, and 10 mg/kg, ip) to elevate PRL secretion was not inhibited by pretreatment with p-chlorophenylalanine, suggesting that RU 24969 stimulates PRL secretion only through activation of postsynaptic 5-HT receptors. To test whether RU 24969 acts centrally, it was injected either icv, through chronic icv cannulae, or peripherally (ip). RU 24969 injected icv significantly stimulated PRL secretion (11-fold) at doses 500-fold lower than the peripherally effective doses (10 micrograms/kg vs. 5 mg/kg), suggesting a role for central 5-HT receptors in the regulation of PRL secretion. In addition, rats pretreated with the 5-HT1C/5-HT2 antagonist LY53857 (icv) significantly inhibited the PRL response if RU 24969 was injected ip, but not icv. The results of these experiments suggest that 5-HT1C or 5-HT2 receptors in the brain participate in the serotonergic stimulation of PRL secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
The purpose of this experiment was to examine the effects of administration of serotonergic (5-HT) agonist and antagonist drugs on run-time to exhaustion (RUN-EXH) in male and female rats. RUN-EXH was reduced (p < 0.05) in a dose related manner by increasing dosages of quipazine dimaleate (QD: general 5-HT agonist) (0-5 mg.kg-1 i.p.) administered immediately prior to exercise (treadmill running at 20 m.min-1 and 5% grade). Conversely, RUN-EXH was increased (p < 0.05) by the greatest dosage of LY 53,857 (LY: 5-HT1C and 5-HT2 antagonist) (1.5 mg.kg-1 i.p.). Drug effects were similar in male and female rats. The negative effects of QD administration on RUN-EXH were not attenuated by administration of the peripherally restricted antagonist, xylamidine tosylate (up to 200 ug.kg-1 i.p.). The results of this investigation indicated that fatigue during prolonged exercise can be influenced by direct pharmacological administration of a serotonergic agonist and antagonist and that the mechanisms underlying these effects are likely to be central (brain) in nature.
The extensive use of performance tests in diet intervention studies mirrors the importance of such a measurement. Although many different endurance performance tests have been used in the past, the majority of these different protocols has never been validated. In this study reproducibility of three different endurance performance tests was evaluated. Thirty well-trained subjects were matched on age, weight, and Wmax and divided into three subgroups. Each group of subjects performed one of three exercise protocols: protocol (A) consisted of cycling at 75% Wmax until exhaustion. In (B) subjects received a preload of 45 min 70% Wmax and then performed as much work as possible in 15 min. (C) consisted of a time trial, in which subjects had to complete a preset amount of work as fast as possible. Each subject performed one of the trials six times. Coefficient of variation (CV) was calculated for each protocol. CV(A) was 26.6%, CV(B) 3.49%, and CV(C) 3.35%. It was concluded that reproducibility of a test at 75% Wmax until exhaustion is poor and these tests are not reliable. Time trial protocols may result in better performance evaluation.
This study investigated the effect of the serotonin receptor antagonist pizotifen on endurance performance during treadmill exercise in humans. Eight healthy men exercised to exhaustion on a treadmill at an intensity corresponding to 70% of their maximal oxygen uptake (VO2max). Pizotifen was administered orally in a 1-mg dose 5 h before the start of exercise. The study was double blind, using a randomized, placebo-controlled crossover design. Oxygen uptake, heart rate, and ratings of perceived exertion were measured and blood samples taken for determination of concentrations of lactate, glucose, amino acids, ammonia, and haematocrit. Measurements were made at intervals of 30 min during the run and at exhaustion. There was no significant difference between the placebo and the pizotifen trials for any of the variables except for the plasma free-tryptophane: branched chain amino acid ratio which was somewhat lower after pizotifen at postexercise. Pizotifen did not increase exercise time to exhaustion, which was even shorter after pizotifen than after placebo in seven out of the eight subjects; the difference between pizotifen and placebo did not reach the level of statistical significance [109.4 (SD 6.7) min after pizotifen versus 119.8 (SD 12.5) min after placebo]. The results do not support the hypothesis that there is a central component to fatigue which is mediated by the serotoninergic neurones.
Fatigue of voluntary muscular effort is a complex phenomenon. To date, relatively little attention has been placed on the role of the central nervous system (CNS) in fatigue during exercise despite the fact that the unwillingness to generate and maintain adequate CNS drive to the working muscle is the most likely explanation of fatigue for most people during normal activities. Several biological mechanisms have been proposed to explain CNS fatigue. Hypotheses have been developed for several neurotransmitters including serotonin (5-HT; 5-hydroxytryptamine), dopamine, and acetylcholine. The most prominent one involves an increase in 5-HT activity in various brain regions. Good evidence suggests that increases and decreases in brain 5-HT activity during prolonged exercise hasten and delay fatigue, respectively, and nutritional manipulations designed to attenuate brain 5-HT synthesis during prolonged exercise improve endurance performance. Other neuromodulators that may influence fatigue during exercise include cytokines and ammonia. Increases in several cytokines have been associated with reduced exercise tolerance associated with acute viral or bacterial infection. Accumulation of ammonia in the blood and brain during exercise could also negatively effect the CNS function and fatigue. Clearly fatigue during prolonged exercise is influenced by multiple CNS and peripheral factors. Further elucidation of how CNS influences affect fatigue is relevant for achieving optimal muscular performance in athletics as well as everyday life.
In this study we examined the effect of a dopamine (DA) precursor (L-DOPA) or a serotonin (5-HT) antagonist (Ritanserin) on time to exhaustion. The study had a double-blind, randomised, placebo controlled and cross-over design. Seven moderately trained men performed three tests to exhaustion at 65% Wattmax. Each test was separated by two weeks to allow washout of the drugs (dose: 4 mg/kg Sinemet, and 0.3 mg/kg Ritanserin). Blood lactate, hematocrit, glucose, ammonia, free fatty acids (FFA), growth hormone (GH) and catecholamines were determined before and after exercise. Time to exhaustion did not differ between the three trials. Most of the parameters measured in this study responded as predicted during cycling to exhaustion in man. DA agonism significantly increased heart rate, lactate, and plasma DA values at rest, while other parameters such as FFA, lactate, plasma noradrenaline (NA) and adrenaline (A), and plasma GH showed the highest absolute levels at exhaustion. Ritanserin did not influence basal glucose and heart rate at rest, but this group showed a much lower increase in plasma catecholamine levels. We conclude that under the present conditions, neither a metabolic precursor of DA nor a specific centrally acting 5-HT2A/2C antagonist, when given in two single doses 24 h and immediately before the experiments, influences the time to exhaustion on a bicycle trial at 65% Wattmax.
We studied the effect of the selective serotonin reuptake inhibitor (SSRI), paroxetine, on basal plasma prolactin concentrations in 11 healthy subjects. Subjects were tested before paroxetine, and after 1 and 3 weeks of treatment (20 mg daily). On each test occasion prolactin levels were sampled before and following administration of a placebo capsule, for a total of 4 h. After 3 weeks paroxetine treatment plasma prolactin levels were significantly higher than those seen either pre-treatment or after 1 week of treatment. In contrast, 1 week of paroxetine treatment did not significantly increase prolactin concentrations over pre-treatment values. Plasma concentrations of paroxetine did not differ between 1 and 3 weeks of treatment. The secretion of plasma prolactin is, in part, under the tonic regulation of serotonergic pathways and the present results therefore support animal experimental data suggesting that SSRIs produce a delayed increase in some aspects of brain serotonin neurotransmission.
Effects of a serotonin re-uptake inhibitor and oral amino acid supplementations on physical and mental performance as well as neuroendocrine variables were investigated. 10 male subjects cycled in four trials until exhaustion. Participants ingested a placebo in trial (T) I, 20 mg paroxetine in T II, 21 g branched-chain amino acids (BCAA) in T III and 20g tyrosine (TYR) in T IV. Heart rate, capillary lactate, plasma insulin, free fatty acids, glucose, serotonin and beta-endorphin did not differ in trials. Plasma ammonia increments during exercise were higher in T III. Plasma BCAA in T III and plasma TYR in T IV were increased after 30 min of exercise according to the supplemented substances. In contrast to all other trials, the ratio of plasma free TRP/BCAA did not increase in T III. Plasma TYR/BCAA was augmented in T IV and decreased in T III after 30 min of exercise, whereas it did not change in T I and II. Plasma prolactin (PRL), growth hormone, cortisol, adrenocorticotropic hormone, norepinephrine and epinephrine increased during all trials. Plasma PRL increments were higher in T IV. Exhaustion was reached earlier in T II. No significant differences were found between other trials. Drive during psychometric testing subsequent to exercise was improved in T III and IV. The results indicate that fatigue during endurance exercise was increased by pharmacological augmentation of the brain serotonergic activity. However, a reduction of 5-HT synthesis via BCAA supplementation did not affect physical fatigue. TYR administration did not alter physical performance either although plasma PRL increments suggest that changes in the monoaminergic system were induced. Precaution is necessary before assuming an ergogenic value of amino acids.
Experiments were carried out to determine the effects of altering the serotonin (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized restrained rats. Local perfusion of the hypothalamus with dialysis solution containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake inhibitor), or high potassium significantly increased both colonic temperature (Tco) and the extracellular concentrations of 5-HT in the hypothalamus. Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks the voltage-dependent sodium channel), zero calcium concentration, or systemic administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and hyperthermic effects, respectively. The results indicate that elevating the 5-HT levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the hypothalamus reduces the endogenous 5-HT release and results in hypothermic effects.
Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.
The present study investigated the effects of hyperthermia on the contributions of central and peripheral factors to the development of neuromuscular fatigue. Fourteen men exercised at 60% maximal oxygen consumption on a cycle ergometer in hot (40°C; hyperthermia) and thermoneutral (18°C; control) environments. In hyperthermia, the core temperature increased throughout the exercise period and reached a peak value of 40.0 ± 0.1°C (mean ± SE) at exhaustion after 50 ± 3 min of exercise. In control, core temperature stabilized at ∼38.0 ± 0.1°C, and exercise was maintained for 1 h without exhausting the subjects. Immediately after the cycle trials, subjects performed 2 min of sustained maximal voluntary contraction (MVC) either with the exercised legs (knee extension) or with a "nonexercised" muscle group (handgrip). The degree of voluntary activation during sustained maximal knee extensions was assessed by superimposing electrical stimulation (EL) to nervus femoralis. Voluntary knee extensor force was similar during the first 5 s of contraction in hyperthermia and control. Thereafter, force declined in both trials, but the reduction in maximal voluntary force was more pronounced in the hyperthermic trial, and, from 30 to 120 s, the force was significantly lower in hyperthermia compared with control. Calculation of the voluntary activation percentage (MVC/MVC + EL) revealed that the degree of central activation was significantly lower in hyperthermia (54 ± 7%) compared with control (82 ± 6%). In contrast, total force of the knee extensors (MVC + force from EL) was not different in the two trials. Force development during handgrip contraction followed the same pattern of response as was observed for the knee extensors. In conclusion, these data demonstrate that the ability to generate force during a prolonged MVC is attenuated with hyperthermia, and the impaired performance is associated with a reduction in the voluntary activation percentage.
The purpose of the present study was to examine the effect of a selective serotonin (5-HT) reuptake inhibitor (SSRI) on exercise performance during a 90 min time trial. Eight well trained male cyclists (VO2max 68.1 +/- 9.5 ml/kg/min) performed three 90 min time trials at 65% Wattmax. Blood samples were collected via an indwelling venous catheter for adrenocorticotropin hormone (ACTH), prolactin (PRL), cortisol, catecholamines, growth hormone (GH) and beta-endorphins. The evening before and the morning of the time trials, the subjects ingested a capsule containing either placebo (lactose) or 20 mg Fluoxetine-HCI (Prozac, Ely Lilly Belgium). A double blind, randomized, placebo controlled, cross-over design was performed. Performance was not influenced by the SSRI. As expected, all blood parameters increased significantly during exercise (p < 0.05). During the SSRI trial most parameters were slightly lower but only significantly for endorphins and PRL (p < 0.05). The results demonstrate that performance is not influenced by an SSRI, although some plasma hormones indicate a central effect of the drug. Surprisingly, the increases in PRL and endorphins were lower during the SSRI trial, meaning that the hormonal modulation during exercise might be regulated by the interaction between neurotransmitters rather than by serotonin alone.
On the basis of an analysis of the skin temperature data on three resting human subjects from 112 experiments, a simple weighting system for computing the mean skin temperature from observations on four areas of the body, namely, chest, arms, thighs, and legs, has been proposed. The proposed system of weighting yields mean skin temperature values identical with the elaborate Hardy-Dubois weighting formula. The value of the medial thigh temperature as an index of the mean skin temperature has also been investigated and discussed.
skin temperature measurement
Submitted on May 20, 1963
The purpose of the experiment was to examine whether selective serotonin (5-HT) re-uptake transporter blockade by paroxetine has any effect on perceived effort (RPE) during exercise or the time to reach volitional fatigue and on the prolactin and cortisol responses during prolonged exercise performed in a warm environment. Eight healthy males performed two cycle rides to exhaustion in a warm (32 degrees C) environment at 60% of maximum oxygen uptake. Paroxetine (20 mg) or placebo was administered 5 h before exercise trials in a randomised double blind fashion. Time to exhaustion was not significantly influenced by administration of paroxetine: median (range) time to exhaustion was 93.3 (76.2-175.0) min on the placebo trial and 92.5 (66.0-151.0) min on the paroxetine trial. Rectal temperature was higher at rest and throughout exercise on the paroxetine trial. The serum concentrations of prolactin and cortisol were determined throughout exercise as peripheral markers of central 5-HT activity. RPE increased over time but was not influenced by paroxetine administration. Prolactin and cortisol levels increased over time but paroxetine administration did not influence the hormone responses during exercise. In conclusion, acute administration of paroxetine failed to alter RPE, exercise capacity or the response of the determined peripheral hormone markers of central 5-HT activity during prolonged exercise in a warm environment.
The effect of serotonin (5-HT)2C receptor blockade on the thermal response and exercise performance during exercise in a warm environment was examined.
Seven endurance-trained, but not heat-acclimatized, individuals (six males and one female) performed two 40-km time trials on a static cycle ergometer in a climatic chamber maintained at a mean (SD) ambient temperature of 35.5 (0.4) degrees C. The 5-HT2C receptor antagonist, pizotifen (1.5 mg), or placebo was administered orally on the evening before and again 6 h before exercise began.
Resting rectal temperature (Tre) was higher (P=0.03) after pizotifen than placebo administration. Tre increased over time during exercise in both trials and was higher (P<0.05) during exercise in the pizotifen trial compared with the placebo trial from 40 to 60 min of exercise. There was no difference in Tre on completion of the time trial. The median times (range) required to complete the 40-km trials were 75.4 (69.0-82.5) and 76.1 (68.0-82.1) min in the pizotifen and placebo trials, respectively. Despite a trend for speed to be slower in the later stages of exercise in the pizotifen trial, performance was not significantly influenced by administration of pizotifen (P=0.86). Resting serum prolactin (Prl) and cortisol concentrations were not different after pizotifen or placebo administration. In both trials, serum Prl and cortisol values increased over time and were increased relative to resting levels in both trials (P<0.01) but were not different between treatments.
The present study suggests that 5-HT may influence body temperature via an effect on the 5-HT2C receptors, but this effect was not sufficient to influence performance.
Nine healthy endurance-trained males were recruited to examine the effect of a dual dopamine/noradrenaline reuptake inhibitor on performance, thermoregulation and the hormonal responses to exercise. Subjects performed four trials, ingesting either a placebo (pla) or 2 x 300 mg bupropion (bup), prior to exercise in temperate (18 degrees C) or warm (30 degrees C) conditions. Trials consisted of 60 min cycle exercise at 55% W(max) immediately followed by a time trial (TT). TT performance in the heat was significantly improved by bupropion (pla: 39.8 +/- 3.9 min, bup: 36.4 +/- 5.7 min; P = 0.046), but no difference between treatments was apparent in temperate conditions (pla: 30.6 +/- 2.2 min, bup: 30.6 +/- 1.9 min; P = 0.954). While TT power output was consistently lower in the heat when compared to temperate conditions, this decrement was attenuated by bupropion. At the end of the TT in the heat, both core temperature (pla 39.7 +/- 0.3 degrees C, bup 40.0 +/- 0.3 degrees C; P = 0.017) and HR (pla 178 +/- 7 beats min(-1), bup 183 +/- 12 beats min(-1); P = 0.039), were higher in the bupropion trial than in the placebo. Circulating pituitary and adrenal hormone concentrations increased throughout exercise in all trials. Circulating serum prolactin was elevated above temperate levels during exercise in a warm environment (P < 0.001). These data indicate that performance in warm conditions is enhanced by acute administration of a dual dopamine/noradrenaline reuptake inhibitor. No such effect was apparent under temperate conditions. It appears that bupropion enabled subjects to maintain a greater TT power output in the heat with the same perception of effort and thermal stress reported during the placebo trial, despite the attainment of a higher core temperature.
Body temperature is decreased by 5-hydroxytryptamine 1A (5-HT1A) agonists and increased by 5-HT2A agonists. The present study determined whether changes in interscapular brown adipose tissue (iBAT) thermogenesis contribute to these effects in conscious unrestrained animals. Male Sprague-Dawley rats were pre-instrumented for measurement of iBAT and core temperature and tail artery blood flow one week before experiments. In the first series of experiments, rats were transferred from warm (25-28°C) to cold (5-10°C) environments. This increased iBAT temperature (+1.3 ± 0.2°C, P < 0.01, n = 7) and reduced tail artery flow. Injection of the 5-HT1A agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin, 0.5 mg/kg, s.c.) reversed the increase in iBAT thermogenesis (-1.5 ± 0.4°C, P < 0.01, n = 6), and decreased core temperature (-1.5 ± 0.4°C, P < 0.01, n = 6). Pre-treatment with WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N- (2-pyridinyl)cyclohexanecarboxamide trihydrochloride), a 5-HT1A antagonist, prevented effects of 8-OH-DPAT. In the second series of experiments, injection of a 5-HT2A agonist, DOI (R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride, 0.1 mg/kg, s.c.) increased both iBAT (+1.9 ± 0.1°C, P < 0.01, n = 7) and core temperatures (+1.4 ± 0.2°C, P < 0.01, n = 7), and decreased tail artery blood flow. Subsequent injection of SR 46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl) propen-1-yl)-phenol, hemifumarate, 0.5 mg/kg, s.c.), a 5-HT2A antagonist, reduced all these changes. Results indicate that activation of 5-HT1A receptors reduces sympathetic outflow to BAT and that activation of 5-HT2A receptors increases this outflow. Changes in core temperature mediated by brain/spinal pathways regulated by 5-HT1A and 5-HT2A receptors reflect coordinated changes in BAT-mediated heat production as well as changes in heat dissipation via the thermoregulatory cutaneous vascular beds.
Acute bupropion (dopamine/noradrenaline reuptake inhibitor) administration significantly improved time trial performance and increased core temperature in the heat (30 degrees C).
The present study was performed to examine the effect of a dopaminergic reuptake inhibitor on exercise capacity and thermoregulation during prolonged exercise in temperate and warm conditions.
Eight healthy well-trained male cyclists participated in this study. Subjects ingested either placebo (PLA; 20 mg) or methylphenidate (MPH; Ritalin; 20 mg) 1 h before the start of exercise in temperate (18 degrees C) or warm (30 degrees C) conditions and cycled for 60 min at 55% Wmax, immediately followed by a time trial (TT; PLA18 and MPH18; PLA30 and MPH30) to measure exercise performance.
MPH did not influence TT performance at 18 degrees C (P = 0.397). TT was completed 16% faster in MPH30 (38.1 +/- 6.4 min) than in PLA30 (45.4 +/- 7.3 min; P = 0.049). In the heat Tcore was significantly higher at rest (P = 0.009), and throughout the TT in MPH30 (P < 0.018), reaching values above 40 degrees C. Throughout MPH30, heart rates were significantly higher (P < 0.05).
These results show that MPH has a clear ergogenic effect that was not apparent in 18 degrees C. The combination of a dopamine reuptake inhibitor and exercise in the heat clearly improved performance and caused hyperthermia without any change in the perception of effort or thermal stress compared with the PLA trial. This response may potentially increase the risk of developing heat illness during exercise in individuals taking drugs of this nature.
Endurance performance in humans: the eVect of a dopamine precursor or a speciWc serotonin (5-HT2A/2C) antagonist Exercise performance is not inXuenced by a 5-HT reup-take inhibitor Central fatigue: the serotonin hypothesis and beyond
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Hypothalamic control of thermoregulation Behavioral studies of the hypothalamus
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Exercise-induced hyperther-mia and hormonal responses to exercise A new weighting system for mean surface temperature of the human body
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Amino acids, brain neurotransmitters and a function link between muscle and brain that is important in sustained exercise Advances in myochemistry
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InXuence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans 5-HT receptors involved in the regulation of hormone secretion Seroto-nergic neurons and 5-HT receptors in the CNS
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Amino acids, brain neurotransmitters and a function link between muscle and brain that is important in sustained exercise
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