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Yawning is a common behavioral event that is observed in humans, as well as other mammals, birds and reptiles. In humans, yawning often occurs just before bed and upon waking up, and is also associated with tedious or boring situations. Although the physiologic roles of yawning have yet to be fully elucidated, the past 50 years of research has led...
Citations
... This suggests the importance of intact neurovascular integrity for an effective heat-removal mechanism by creating spatial gradients in brain temperature. It is also worth mentioning that yawning and stretching are compensatory thermoregulatory mechanisms against increased brain temperature mediated by various neurotransimitters such as acetylcholine, serotonin, dopamin and GABA [35,36]. This is suggested by the same authors showing that heavy nasal breathing terminated the yawning reflex by reducing the brain temperature [37]. ...
... In light of all this evidence, it is crucially important to measure brain temperature for a better understanding of the pathophysiology of neurodegeneration. Although the MRS method may involve some patient-dependent calculation errors, such as tissue susceptibility changes and body movements [35], it can still represent a unique noninvasive diagnostic alternative for measuring and monitoring brain temperature in healthy and disease conditions. ...
Brain temperature determines not only an individual's cognitive functionality but also the prognosis and mortality rates of many brain diseases. More specifically, brain temperature not only changes in response to different physiological events like yawning and stretching, but also plays a significant pathophysiological role in a number of neurological and neuropsychiatric illnesses. Here, we have outlined the function of brain hyperthermia in both diseased and healthy states, focusing particularly on the amyloid beta aggregation in Alzheimer's disease.
... Yawning is one of the symptoms reported by individuals with migraine during the premonitory phase [39]. Several hypothalamic nuclei have been implicated in the mediation of yawning, including the dorsomedial nucleus, ventromedial nucleus, and anterior hypothalamus, but mainly the paraventricular nucleus (PVN) [40][41][42]. Yawning behavior in rodents can be elicited through a multitude of mechanisms but include especially dopaminergic agonists. In this study, we used apomorphine, a dopaminergic D1/2 agonist to demonstrate yawning (i.e., as a positive control) [43]. ...
Background
The migraine premonitory phase is characterized in part by increased thirst, urination and yawning. Imaging studies show that the hypothalamus is activated in the premonitory phase. Stress is a well know migraine initiation factor which was demonstrated to engage dynorphin/kappa opioid receptors (KOR) signaling in several brain regions, including the hypothalamus. This study proposes the exploration of the possible link between hypothalamic KOR and migraine premonitory symptoms in rodent models.
Methods
Rats were treated systemically with the KOR agonist U-69,593 followed by yawning and urination monitoring. Apomorphine, a dopamine D1/2 agonist, was used as a positive control for yawning behaviors. Urination and water consumption following systemic administration of U-69,593 was also assessed. To examine if KOR activation specifically in the hypothalamus can promote premonitory symptoms, AAV8-hSyn-DIO-hM4Di (Gi-DREADD)-mCherry viral vector was microinjected into the right arcuate nucleus (ARC) of female and male KORCRE or KORWT mice. Four weeks after the injection, clozapine N-oxide (CNO) was administered systemically followed by the assessment of urination, water consumption and tactile sensory response.
Results
Systemic administration of U-69,593 increased urination but did not produce yawning in rats. Systemic KOR agonist also increased urination in mice as well as water consumption. Cell specific Gi-DREADD activation (i.e., inhibition through Gi-coupled signaling) of KORCRE neurons in the ARC also increased water consumption and the total volume of urine in mice but did not affect tactile sensory responses.
Conclusion
Our studies in rodents identified the KOR in a hypothalamic region as a mechanism that promotes behaviors consistent with clinically-observed premonitory symptoms of migraine, including increased thirst and urination but not yawning. Importantly, these behaviors occurred in the absence of pain responses, consistent with the emergence of the premonitory phase before the headache phase. Early intervention for preventive treatment even before the headache phase may be achievable by targeting the hypothalamic KOR.
... being a second born twin). These findings, although preliminary and based only on behavioral data, might indicate that several distinct neuropharmacological pathways that have been found to be involved in yawn modulation [64] are already observable in preterm neonates. Furthermore, demographic variables, including gender and age measures (GA, CH and PMA) were not found to affect yawning frequencies, suggesting that the observed pattern can be generalized to healthy preterm neonates from at least 32 weeks PMA. ...
... Future research should address some limitations of the present study, by investigating the specific effect of different behavioral states, including both quiet and active sleep, as well as the potential associations between yawning frequencies and state transitions or instability. Moreover, additional studies will be needed in order to directly test the hypothesis that stress and hunger-related modulations in neonates are in fact ascribable to cholinergic and ACTH-mediated pathways, as postulated by Collins and Eguibar [64]. In particular, further research is needed to confirm whether the effect of birth order on yawning rates in twins is due to stress-related factors associated with birth or to other variables and whether hunger or stress-related modulation of yawning can be explained in terms of brain thermoregulation. ...
Yawning is a long neglected behavioral pattern, but it has recently gained an increasing interdisciplinary attention for its theoretical implications as well as for its potential use as a clinical marker, with particular regard to perinatal neurobehavioral assessment. The present study investigated the factors affecting yawning frequencies in hospitalized preterm neonates (N = 58), in order to distinguish the effects of hunger and sleep-related modulations and to examine the possible impact of demographic and clinical variables on yawning frequencies. Results showed that preterm neonates yawned more often before than after feeding, and this modulation was not explained by the amount of time spent in quiet sleep in the two conditions. Moreover, second born twins, known to be more prone to neonatal mortality and morbidity, showed increased yawning rates compared to first born twins. Overall, our results are consistent with the hypothesis that yawning frequencies in preterm neonates are modulated by separate mechanisms, related e.g. to hunger, vigilance and stress. These findings, although preliminary and based only on behavioral data, might indicate that several distinct neuropharmacological pathways that have been found to be involved in yawn modulation in adults are already observable in preterm neonates.
... One of these symptoms, yawning, has relevance for the overarching study hypothesis that abnormal dopamine signaling is responsible for unmanaged opioid withdrawal symptoms. Yawning is considered the strongest in vivo measure of D2-receptor family binding affinity outside of tissue analyses (Collins & Eguibar, 2010;Krestel et al., 2018). Additionally, yawning is also impacted by serotonergic activity and is a classic symptom of serotonin syndrome (Krestel et al., 2018). ...
Successful management of opioid withdrawal improves long-term treatment outcomes and reduces opioid use-related morbidity and mortality. Mechanistically supported pharmacotherapeutic approaches are needed to effectively manage acute and protracted opioid withdrawal. Buspirone is a D2 antagonist and 5-HT1a agonist that may decrease opioid withdrawal. Individuals (n = 15) admitted to a residential treatment center for opioid use disorder (OUD) were enrolled into a double-blind randomized clinical trial to assess the efficacy and acceptability of buspirone (45 mg/day) as an adjunctive medication to buprenorphine-assisted, supervised opioid withdrawal. Participants completed daily questionnaires which consisted of the Subjective Opiate Withdrawal Scale (SOWS) and a consensus sleep diary, which assessed total sleep time, time to sleep onset, and sleep quality. Total SOWS scores, individual opioid withdrawal symptoms and sleep outcomes were assessed between treatment groups (Placebo and Buspirone) and over time in a repeated measures linear mixed model. Total SOWS scores significantly decreased across study phases for both groups but decreased to a greater extent among individuals assigned to buspirone during both the first and second week of stable buspirone. Greater decreases in withdrawal were observed during Week 2 of stable buspirone relative to Week 1 of stable buspirone. Participants also reported significant increases in sleep duration and significant decreases in latency to sleep onset. This study provides further support that buspirone can help mitigate opioid withdrawal during a supervised opioid taper. Buspirone may confer unique benefits during protracted withdrawal periods.
... During the last decades, our understanding of the neurophysiological paths involved in yawn generation and modulation, as well as of the conditions and stimuli that can affect yawning behavior has significantly increased. This led to the identification of three neurophysiological pathways involved in yawning regulation, namely a cholinergic, an oxytocinergic and an ACTH-mediated pathway [3,4], as well as to the characterization of different classes of conditions affecting yawning patterns. In particular, human yawning behavior has been found to be modulated by a vast set of processes and conditions, including circadian rhythms [5,6], hunger [7,8], thermoregulation [2,9,10] emotional or social distress [11,12], pain [13,14], drowsiness [15] neurological conditions [16,17], and the intake of different drugs [3,18,19]. ...
... In term of the hormonal profiles that have been argued to be associated with various classes of yawning-modulating factors, we might hypothesize the Still-Face effect highlighted for both sexes to be ACTH-related, being associated with a condition of mild stress, while the higher incidence of yawning in females may indicate a differential oxytocinergic modulation of yawning behavior. This finding could in fact be related with the phenomenon of mini-puberty, which determines a transient sex-specific activation of the hypothalamic-pituitary-gonadal axis, known to be involved in yawn modulation [4], mainly during the first 6 postnatal months [65][66][67][68]. ...
The last decades have seen an increasing interest in the phenomenon of yawning and the dynamics of its modulation, yet no widespread consensus exists on its origins and potential functions. Although most scholars have focused on its potential physiological functions, e.g., related to thermoregulation, arousal modulation or cortisol levels and distress, an emerging line of research has been also investigating the social implications of yawning, including its hypothesized relationship with empathy. In order to explore the dynamics of yawning modulation in infants, we investigated whether a social perturbation–like the one induced by the Face to Face Still Face paradigm, a procedure designed to assess socio-emotional regulation in infants–affects yawning and self-touch hand movements behavior in three-months old infants. As the Still Face episode represents a source of mild distress, we hypothesized that during this phase yawns would be more frequent. Moreover, through the use of path analysis, we investigated potential dynamics of facilitation, inhibition or covariance between the frequencies of these behavioral patterns. Our results showed a sharp increase in self-touch hand movements as well as in the likelihood of yawning during the stressful phase of the procedure (still-face) compared with the two minutes of face-to-face interaction and the reunion episode. Regressions also showed a higher incidence of yawns among girls, consistently with the hypothesis that the analysis of yawning behavior might capture subtle differences in regulatory strategies of infants, possibly related to the transient sex-specific activation of the hypothalamic-pituitary-gonadal axis known as mini-puberty. The path analysis showed a greater consistency between the frequencies of self-touch hand movements during the three episodes of the procedure, compared with yawning. This finding could be a result of distinct yawning-regulating mechanisms being at play in different conditions, e.g., a modulation related to stress and one to social interaction. Taken together, these results suggest that human yawning regulation is an irreducibly complex and multifaceted phenomenon since early age. Moreover, the gender differences highlighted might suggest an early diversification in yawning modulation.
... In the present study, we used two selectively inbred sublines from Sprague-Dawley (SD) rats that differed in terms of the frequency of spontaneous yawning. Specifically, the high-yawning (HY) subline had a mean of 20 yawns/h, and the low-yawning (LY) subline had just 2 yawns/h [8,46]. HY male rats also had more spontaneous penile erections, and 50% of these erections were temporally associated with a yawn within a time window of just 3 min [13,23]. ...
... In this context, it is relevant that our results, obtained with intracerebroventricular (i.c.v.) injections of different doses of oxytocin, induced higher frequencies of yawning and penile erections in HY rats with respect to LY and SD rats [10]. These effects are mediated by activity in the paraventricular nucleus of the hypothalamus [2,8]. ...
Mating behavior in rodents can modulate pain sensations in both sexes. In males, the execution of mounts, intromissions, and ejaculations induced a progressive increase in their vocalization thresholds induced by tail shocks and other types of noxious stimuli.
We selectively inbred two sublines from Sprague-Dawley (SD) rats that differed in their spontaneous yawning frequency. The high-yawning (HY) subline had a mean of 20 yawns/h and a different pattern of sexual behavior characterized by longer interintromission intervals and more sexual bouts that delayed ejaculation. The low-yawning (LY) subline and SD rats yawned as a mean 2 and 1 yawns/h, respectively.
So, we determine mating-induced analgesia in HY, LY, and SD male rats by measuring vocalization thresholds in response to noxious electric tail shocks. Our results showed that the magnitude of mating-induced analgesia was lower in HY and LY rats with respect to SD rats. When the rats performed different components of male sexual pattern, both sublines exhibited a significantly lower increase in their vocalization thresholds with respect to SD rats—being sublines less responsive regarding mating-induced analgesia. Pain modulation mechanisms depend on responses to stress, so the low levels of analgesia obtained in the yawning sublines may be due either to differences in their response to stress in other paradigms, or to atypical performance of male sexual behavior during mating, an event which as a stressful event in rats.
Therefore, the yawning sublines are a suitable model for analyzing how a different temporal pattern in the display of male sexual behavior affects analgesia mechanisms. Our results concur with Wistar rats with different endophenotypes that could apply to humans as well.
... Dopamine elicits yawning through activation of D3 receptors in the hypothalamic paraventricular nucleus, whereas opioid agents inhibit yawning through activation of µ -opioid receptors in the paraventricular nucleus [2][3][4]. Our patient was subjected to a treatment regime with the weak oral µ -opioid-receptor agonist tilidine (50 mg + 4 mg naloxone, slow release preparation) before each planned bout of exercise; this treatment entailed that strain of the right leg did not trigger yawning and fatigue anymore [1]. ...
... Significant advances in understanding the genesis of yawning have not yet fully elucidated its physiological role [14,15]. The release of dopamine and the subsequent activation of D3 receptors in the diencephalon play a key role in regulating yawning [2][3][4]. Yawning has been observed in different neurological disorders [15,16], e. g. in the prodromal phase of migraine [17,18] or together with parakinesia brachialis oscitans in stroke patients [19,20]. Even so, yawning is rarely a major feature of neurological disorders. ...
A 60-year-old man suffering from recurrent attacks of yawning-fatigue-syndrome, triggered by mild exercise of his right leg since a temporary lumbar disc herniation 9 years ago, was initially treated with the oral µ-opioid-receptor agonist tilidine before each bout of exercise (see Dibaj et al. 2019 JAMA Neurology 2019;77:254). During the first few months, this treatment continuously prolonged the time without exercise-triggered yawning and fatigue. In the next few months of treatment, exercise was increased in a graded manner to alleviate the yawning-fatigue-syndrome. The number of repetitions of the physical exercises was gradually increased without taking the opioid beforehand. After several months, almost the same effort level without medication could be achieved by graded activity as before under the influence of opioid medication. Graded physical activity can thus disrupt complex pathophysiological mechanisms leading to yawning and fatigue.
... Globally, the current latent inhibition theories and experimental evidence suggest that high stimulus familiarization (e.g., sugar), induced after long intervals and different contexts, involves a broader range of behavioral and learning processes that are recruited during chronic sugar exposure and result in enhanced appetitive memory (De la Casa and Lubow 2001;Hajnal and Norgren 2001;Colantuoni et al. 2002). Thus, the inability of the HY and LY sublines to develop latent inhibition of CTA after long-term sugar exposure could be related to the time/context processes inherently altered in the behavioral traits that have arisen as a result of long inbreeding process of these sublines (Urba-Holmgren et al. 1990;Collins and Eguibar 2010). In this regard, there is evidence in rodent models that long-term consumption of hedonic tastes, like sucrose, induces significant physiological changes that involve several neurotransmitter systems (Colantuoni et al. 2001;Rada et al. 2010;Pritchett and Hajnal 2011;Bello et al. 2014;Caynas-Rojas et al. 2018). ...
Yawning is a stereotypical behavior pattern commonly associated with other behaviors such as grooming, sleepiness, and arousal. Several differences in behavioral and neurochemical characteristics have been described in high-yawning (HY) and low-yawning (LY) sublines from Sprague–Dawley (SD) rats that support they had changes in the neural mechanism between sublines. Differences in behavior and neurochemistry observed in yawning sublines could also overlap in processes needed during taste learning, particularly during conditioned taste aversion (CTA) and its latent inhibition. Therefore, the aim of this study was to analyze taste memory differences, after familiarization to novel or highly sweet stimuli, between yawning sublines and compare them with outbred SD rats. First, we evaluated changes in appetitive response during long-term sugar consumption for 14 days. Then, we evaluated the latent inhibition of CTA strength induced by this long pre-exposure, and we also measured aversive memory extinction rate. The results showed that SD rats and the two sublines developed similar CTA for novel sugar and significantly stronger appetitive memory after long-term sugar exposure. However, after 14 days of sugar exposure, HY and LY sublines were unable to develop latent inhibition of CTA after two acquisition trials and had a slower aversive memory extinction rate than outbreed rats. Thus, the inability of the HY and LY sublines to develop latent inhibition of CTA after long-term sugar exposure could be related to the time/context processes involved in long-term appetitive re-learning, and in the strong inbreeding that characterizes the behavioral traits of these sublines, suggesting that inbreeding affects associative learning, particularly after long-term exposure to sweet stimuli which reflects high familiarization.
... Yawning induced by D2-agonists is suppressed by D2-like antagonists as expected. However, D2-agonist-induced yawning is also inhibited by anticholinergics [35,48]. Cholinesterase inhibitors and muscarinic receptor agonists can also induce yawning which can be suppressed by anticholinergics but not dopamine receptor antagonists [36,48]. ...
... However, D2-agonist-induced yawning is also inhibited by anticholinergics [35,48]. Cholinesterase inhibitors and muscarinic receptor agonists can also induce yawning which can be suppressed by anticholinergics but not dopamine receptor antagonists [36,48]. Thus, the dopaminergic effect on yawning is likely executed by downstream cholinergic transmission, probably via M1 muscarinic receptors. ...
Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson’s disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD. Some people with PD describe autonomic symptoms at the time of diagnosis suggesting that autonomic dysfunction is a common feature of prodromal PD. Furthermore, subtle motor signs may be present and emerge prior to the time of diagnosis. We present a series of patients who, in the prodromal phase of PD, experienced the emergence of tremor initially only while yawning or straining at stool and discuss how early involvement of autonomic brainstem nuclei could lead to these previously unreported phenomena. The hypothalamic paraventricular nucleus (PVN) plays a central role in autonomic control including bowel/bladder function, cardiovascular homeostasis and yawning and innervates multiple brainstem nuclei involved in autonomic functions (including brainstem reticular formation, locus ceruleus, dorsal raphe nucleus and motor nucleus of the vagus). The PVN is affected in PD and evidence from related phenomena suggest that the PVN could increase tremor either by increasing downstream cholinergic activity on brainstem nuclei such as the reticular formation or by stimulating the locus ceruleus to activate the cerebellothalamocortical network via the ventrolateral nucleus of the thalamus. Aberrant cholinergic/noradrenergic transmission between these brainstem nuclei early in PD couldlead to tremor before the emergence of other parkinsonian signs, representing an early clinical clue to prodromal PD.
... Yawning is a stereotyped behavioral pattern that is characterized by deep inspiration followed by short expiration across all vertebrate species (Barbizet, 1958;Argiolas and Melis, 1998;Collins and Eguibar, 2010). In mammals, including rats, yawning frequency is very low, approximately 1 yawn/h (Baenninger, 1997). ...
... Yawning behavior is regulated by several neurotransmitters, including cholinergic, muscarinic, or D 2 -like dopaminergic agonists; it is inhibited by opioids and GABAergic mechanisms (for review, see Argiolas and Melis, 1998;Collins and Eguibar, 2010); and it is increased by the central administration of adrenocorticotrophic, α-melanocyte-stimulating hormone (MSH), oxytocin, and prolactin peptides and inhibited by bombesin (Argiolas and Melis, 1998;Díaz-Romero et al., 2002;Collins and Eguibar, 2010). Among all of these neurotransmitters and neuromodulators, the dopaminergic system, through D 2 -like receptors, is the most potent inducer of yawning and penile erections, acting in the paraventricular nucleus (PVN) of the hypothalamus (Sanna et al., 2012), and the motor output is regulated by the striatum (Dourish and Cooper, 1990). ...
... Yawning behavior is regulated by several neurotransmitters, including cholinergic, muscarinic, or D 2 -like dopaminergic agonists; it is inhibited by opioids and GABAergic mechanisms (for review, see Argiolas and Melis, 1998;Collins and Eguibar, 2010); and it is increased by the central administration of adrenocorticotrophic, α-melanocyte-stimulating hormone (MSH), oxytocin, and prolactin peptides and inhibited by bombesin (Argiolas and Melis, 1998;Díaz-Romero et al., 2002;Collins and Eguibar, 2010). Among all of these neurotransmitters and neuromodulators, the dopaminergic system, through D 2 -like receptors, is the most potent inducer of yawning and penile erections, acting in the paraventricular nucleus (PVN) of the hypothalamus (Sanna et al., 2012), and the motor output is regulated by the striatum (Dourish and Cooper, 1990). ...
Yawning is a stereotyped behavioral pattern characterized by wide opening of the mouth associated with deep inspiration followed by short expiration. All vertebrate species yawn, but with low frequencies. We obtained two sublines of Sprague–Dawley (SD) rats by a strict inbreeding process: one with a high-yawning frequency (HY) of 20 yawns/h, which is one order of magnitude higher with respect to the low-yawning frequency (LY) subline, with 2 yawns/h. Outbred SD rats had a yawning frequency of 1 yawn/h. HY dams had a different organization of maternal care with respect to that displayed by LY and SD dams because HY dams constructed lower quality nests and had more re-retrieving and atypical retrieving. The aim of this study was to analyze the changes in maternal care using in- and cross-fostering between the sublines and SD dams and to measure spontaneous and dopaminergic-induced yawning, penile erections, grooming and scratching bouts. We also measured the expression of dopamine D2 receptors in the striatum using Western blot analysis. Our results showed that HY male rats reared by SD or LY dams did not significantly differ in yawning frequencies with respect to HY male rats reared by mothers of their own phenotype. Maternal care did not differ between sublines and SD dams independent of the litter they reared. However, LY rats reared by HY dams showed a significant increase in the number of spontaneous penile erections. Importantly, in-fostered HY male rats had the highest number of yawns induced by systemic administration of (−)-quinpirole supporting that higher maternal care display can influence the frequency of dopaminergic-induced yawning. In fact HY male rats in all conditions yawned more than did LY and SD male rats independent of the dam that raised them supporting a strong influence of genetic background. However SD male rats raised by LY dams showed significantly increased the dopamine D2 receptor expression. In conclusion, maternal care and the environmental nest conditions during the lactation period did not change the phenotypic characteristics of the yawning sublines supporting that their genetic background is fundamental for the expression of spontaneous or dopaminergic-induced yawning.
