No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
High doses of oxytocin cause sedation and low doses cause an anxiolytic-like effect in male rats
Abstract
The aim of the present investigation was to explore dose relationships for effects of oxytocin on spontaneous motor activity in the rat. Oxytocin in doses from 1-1000 micrograms/kg was given SC to male Sprague-Dawley rats, and spontaneous motor behavior was measured by means of photocell-operated open-field observations. In the rats treated with low doses of oxytocin (1-4 micrograms/kg), there was a decrease in peripheral locomotor activity. With increasing doses (250-1000 micrograms/kg), there were clear signs of sedative effects as indicated by a suppression of locomotor activity and rearing. The time course for the effect of oxytocin on peripheral activity (1 microgram/kg) and rearing (1 mg/kg) was tested. A maximal effect was obtained within 1 h and, thereafter, the behavior gradually returned to normal within 24 h. This spectrum of effects caused by oxytocin was similar to that of midazolam but different from that induced by raclopride.
... Animals received daily i.p. injections for 10 days between 9:00 and 11:00. As oxytocin injections can cause what appears to be sedation (e.g., Uvnäs-Moberg et al., 1994; the current study), we monitored "sedation" 5-10 min post-injection over the course of the 10 days using a binary score (0 = no sedation, 1 = sedation indicated by a clear lack of locomotor activity and rearing, eyes closed and rats appearing asleep). In addition, animals were behaviourally tested 2 h after injection on day 9 to avoid confounding sedative and/or muscular effects of oxytocin that would affect locomotion (Elabd et al., 2014;Hess et al., 2016;Leong et al., 2016;Uvnäs-Moberg et al., 1994). ...
... As oxytocin injections can cause what appears to be sedation (e.g., Uvnäs-Moberg et al., 1994; the current study), we monitored "sedation" 5-10 min post-injection over the course of the 10 days using a binary score (0 = no sedation, 1 = sedation indicated by a clear lack of locomotor activity and rearing, eyes closed and rats appearing asleep). In addition, animals were behaviourally tested 2 h after injection on day 9 to avoid confounding sedative and/or muscular effects of oxytocin that would affect locomotion (Elabd et al., 2014;Hess et al., 2016;Leong et al., 2016;Uvnäs-Moberg et al., 1994). On day 10, brains were collected 30 mins after oxytocin injection. ...
... Injections of oxytocin caused "sedation" observed 5-10 min postinjection (Uvnäs-Moberg et al., 1994). We calculated a "sedation" score using a binary score (0 = no sedation, 1 = sedation indicated by a clear lack of locomotor activity and rearing, eyes closed and rats appearing asleep) over the course of 10 days for a maximum possible score of 10. ...
Oxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZAN™ (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZAN™ (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17β-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZAN™ reduced sedation observed post-injection and increased some central effects (oxytocin levels in the hypothalamus and ventral hippocampus neurogenesis) relative to oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that oxytocin does not promote social investigation in females.
... Animals received daily i.p. injections for 10 days between 9:00 and 11:00. As oxytocin injections can cause what appears to be sedation (e.g., Uvnäs-Moberg et al., 1994; the current study), we monitored "sedation" 5-10 min post-injection over the course of the 10 days using a binary score (0 = no sedation, 1 = sedation indicated by a clear lack of locomotor activity and rearing, eyes closed and rats appearing asleep). In addition, animals were behaviourally tested 2 h after injection on day 9 to avoid confounding sedative and/or muscular effects of oxytocin that would affect locomotion (Elabd et al., 2014;Hess et al., 2016;Leong et al., 2016;Uvnäs-Moberg et al., 1994). ...
... As oxytocin injections can cause what appears to be sedation (e.g., Uvnäs-Moberg et al., 1994; the current study), we monitored "sedation" 5-10 min post-injection over the course of the 10 days using a binary score (0 = no sedation, 1 = sedation indicated by a clear lack of locomotor activity and rearing, eyes closed and rats appearing asleep). In addition, animals were behaviourally tested 2 h after injection on day 9 to avoid confounding sedative and/or muscular effects of oxytocin that would affect locomotion (Elabd et al., 2014;Hess et al., 2016;Leong et al., 2016;Uvnäs-Moberg et al., 1994). On day 10, brains were collected 30 mins after oxytocin injection. ...
... Injections of oxytocin caused "sedation" observed 5-10 min postinjection (Uvnäs-Moberg et al., 1994). We calculated a "sedation" score using a binary score (0 = no sedation, 1 = sedation indicated by a clear lack of locomotor activity and rearing, eyes closed and rats appearing asleep) over the course of 10 days for a maximum possible score of 10. ...
Oxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZAN™ (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZAN™ (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17β-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZAN™ reduced sedation observed post-injection and increased some central effects (oxytocin levels in the hypothalamus and ventral hippocampus neurogenesis) relative to oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and contributes to the evidence that oxytocin is not a prosocial hormone in both sexes.
... Another possibility is that the effects of exogenous oxytocin in females are influenced by reproductive hormones that fluctuate throughout the estrous cycle and have complex interactions with the oxytocin system as demonstrated in a recent review of the literature (Jirikowski et al., 2017). Previous studies demonstrated that intracerebroventricular (ICV) oxytocin administration produced an anxiolytic-like response in males (Uvnäs-Moberg et al., 1994;Ring et al., 2006;Yoshida et al., 2009) and in estrogen-treated, but not vehicle-treated, ovariectomized females (McCarthy et al., 1996). However, unknown is the effect of ICV oxytocin administration in naturally cycling females, across the estrous cycle and in ovariectomized females with progesterone supplementation. ...
... The observation that the magnitude of differences in the elevated zero maze measures following ICV oxytocin administration was greater in males is consistent with previous studies that reported anti-stress effects of oxytocin (Uvnäs-Moberg et al., 1994;Windle et al., 1997;Ring et al., 2006;Yoshida et al., 2009;Ring et al., 2010). For example, Windle et al. found that oxytocin (1-100 ng/h, ICV) inhibited stress-induced increases in corticosterone levels in male rats (Windle et al., 1997) and Ring et al. found that oxytocin (1 μg/mouse, ICV) (Ring et al., 2006) and peripheral administration of the oxytocin receptor agonist, WAY-267464 (Ring et al., 2010), reduced measures of anxiety-like behavior in male mice. ...
Anxiety and depression are highly prevalent psychiatric disorders, affecting approximately 18% of the United States population. Evidence indicates that central oxytocin mediates social cognition, social bonding, and social anxiety. Although it is well-established that oxytocin ameliorates social deficits, less is known about the therapeutic effects of oxytocin in non-social contexts. We hypothesized that positive effects of oxytocin in social contexts are attributable to intrinsic effects of oxytocin on neural systems that are related to emotion regulation. The present study investigated the effect of intracerebroventricular (ICV) oxytocin administration (i.e., central action) on anxiety- and depression-like behavior in C57Bl/6J mice using non-social tests. Male and female mice received an ICV infusion of vehicle or oxytocin (100, 200, or 500 ng), then were tested in the elevated zero maze (for anxiety-like behavior) and the tail suspension test (for depression-like behavior). Oxytocin dose-dependently increased open zone occupancy and entries in the elevated zero maze and reduced immobility duration in the tail suspension test in both sexes. Oxytocin decreased anxiety and depression-like behavior in male and female mice. The observed effect of oxytocin on anxiolytic-like behavior appeared to be driven by the males. Given the smaller anxiolytic-like effect of oxytocin in the female mice and the established interaction between oxytocin and reproductive hormones (estrogen and progesterone), we also explored whether oxytocin sensitivity in females varies across estrous cycle phases and in ovariectomized females that were or were not supplemented with estrogen or progesterone. Oxytocin reduced anxiety-like behavior in female mice in proestrus/estrus, ovariectomized females (supplemented or not with estrogen or progesterone), but not females in metestrus/diestrus. Additionally, oxytocin reduced depression-like behavior in all groups tested with slight differences across the various hormonal statuses. These results suggest that the effect of oxytocin in depression- and anxiety-like behavior in mice can be influenced by sex and hormonal status.
... Our results offer insight into the use of OXT as an effective anxiolytic to diminish the effect of stress on alcohol addiction-related behaviors. Previous studies have shown that OXT may have anxiolytic effects in animals [30,46] and humans [47,48]. For example, intranasal administration of OXT reduces anxiety related to public speaking situations in humans [11], and chronic intranasal administration may alleviate exaggerated threat reactivity in subjects with elevated anxiety levels [49]. ...
... For example, intranasal administration of OXT reduces anxiety related to public speaking situations in humans [11], and chronic intranasal administration may alleviate exaggerated threat reactivity in subjects with elevated anxiety levels [49]. Peripheral administration of OXT reduces anxiety-like behaviors of animals when placed in novel environments [46] and diminishes the overall anxiety-related behaviors across several behavioral tests of anxiety [50]. Furthermore, stimulation of endogenous oxytocin release significantly attenuated freezing behavior in a fear conditioning paradigm [30]. ...
Alcohol use disorder is a significant public health concern, further exacerbated by an increased risk of relapse due to stress. In addition, factors such as biological sex may contribute to the progression of addiction, as females are especially susceptible to stress-induced relapse. While there have been many studies surrounding potential pharmacological interventions for male stress-induced ethanol reinstatement, research regarding females is scarce. Recently, the neuropeptide oxytocin has gained interest as a possible pharmacological intervention for relapse. The present study examines how oxytocin affects yohimbine-induced reinstatement of ethanol-seeking in female rats using a self-administration paradigm. Adult female rats were trained to press a lever to access ethanol in daily self-administration sessions. Rats then underwent extinction training before a yohimbine-induced reinstatement test. Rats administered with yohimbine demonstrated significantly higher lever response indicating a reinstatement of ethanol-seeking behavior. Oxytocin administration, both systemically and directly into the central amygdala, attenuated the effect of yohimbine-induced reinstatement of ethanol-seeking behavior. The findings from this study establish that oxytocin is effective at attenuating alcohol-relapse behavior mediated by the pharmacological stressor yohimbine and that this effect is modulated by the central amygdala in females. This provides valuable insight regarding oxytocin’s potential therapeutic effect in female stress-induced alcohol relapse.
... This brain structure has a large number of oxytocin receptors involved, among others, in fear behavior inhibition (2,39) and stress-coping behavior (40). Moreover, subcutaneous (41) and intracerebroventricular (42) oxytocin administration reduces anxiety- like behavior in rats. Also, Windle et al., 1997 (42) reported a reduction of rearing by i.c.v. ...
... On the other hand, the OXTR antagonist decreased vertical exploration (assessed as rearing episodes in the EPM test) independently of the hydration state of the animal. In addition to demonstrating that oxytocin receptor blockade was efficient, this result indicates that although the general action of oxytocin on the central nervous system can decrease exploration (41,43), the activation of CeA oxytocin receptors seems to stimulate exploration, since their blocked reduced rearing. On the other hand, the WD-induced alteration in locomotory activity may involve other brain nuclei. ...
Introduction
Vasopressin (AVP) and oxytocin (OXT) are neuropeptides produced by magnocellular neurons (MCNs) of the hypothalamus and secreted through neurohypophysis to defend mammals against dehydration. It was recently demonstrated that MCNs also project to limbic structures, modulating several behavioral responses.
Methods and Results
We found that 24 h of water deprivation (WD) or salt loading (SL) did not change exploration or anxiety-like behaviors in the elevated plus maze (EPM) test. However, rats deprived of water for 48 h showed reduced exploration of open field and the closed arms of EPM, indicating hypoactivity during night time. We evaluated mRNA expression of glutamate decarboxylase 1 (Gad1), vesicular glutamate transporter 2 (Slc17a6), AVP (Avpr1a) and OXT (Oxtr) receptors in the lateral habenula (LHb), basolateral (BLA) and central (CeA) amygdala after 48 h of WD or SL. WD, but not SL, increased Oxtr mRNA expression in the CeA. Bilateral pharmacological inhibition of OXTR function in the CeA with the OXTR antagonist L-371,257 was performed to evaluate its possible role in regulating the EPM exploration or water intake induced by WD. The blockade of OXTR in the CeA did not reverse the hypoactivity response in the EPM, nor did it change water intake induced in 48-h water-deprived rats.
Discussion
We found that WD modulates exploratory activity in rats, but this response is not mediated by oxytocin receptor signaling to the CeA, despite the upregulated Oxtr mRNA expression in that structure after WD for 48 h.
... 9:30-10:30am. As oxytocin injections can cause sedation-like effects (Uvnäs-Moberg et al., 1994;Hess et al., 2016;Duarte-Guterman et al., 2020), all offspring were monitored for 30 min after injections for sedation-like effects using a 3-point scale: 0 = no sedation, 1 = mild sedation-like, 2 = complete sedation-like, at three different time points (5 min, 10 m, and 30 min post-injection). OT has effects on muscles to both constrict and produce relaxation depending on the types of muscle and muscle tone (Altura and Altura, 1984;Wooldridge et al., 2002), and it is possible that the sedation-like effects seen after OT (Uvnäs-Moberg et al., 1994;Hess et al., 2016;Duarte-Guterman et al., 2020) are attributable to OT's effects on muscles. ...
... As oxytocin injections can cause sedation-like effects (Uvnäs-Moberg et al., 1994;Hess et al., 2016;Duarte-Guterman et al., 2020), all offspring were monitored for 30 min after injections for sedation-like effects using a 3-point scale: 0 = no sedation, 1 = mild sedation-like, 2 = complete sedation-like, at three different time points (5 min, 10 m, and 30 min post-injection). OT has effects on muscles to both constrict and produce relaxation depending on the types of muscle and muscle tone (Altura and Altura, 1984;Wooldridge et al., 2002), and it is possible that the sedation-like effects seen after OT (Uvnäs-Moberg et al., 1994;Hess et al., 2016;Duarte-Guterman et al., 2020) are attributable to OT's effects on muscles. ...
Untreated perinatal depression can have severe consequences for the mother and her children. However, both the efficacy to mothers and safety to exposed infants of pharmacological antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been questioned. We previously reported that maternal SSRI exposure increased hippocampal IL-1β levels, which may be tied to limited efficacy of SSRIs during the postpartum to the dam but is not yet known whether maternal postpartum SSRIs affect the neuroinflammatory profile of adult offspring. In addition, although controversial, perinatal SSRI exposure has been linked to increased risk of autism spectrum disorder (ASD) in children. Oxytocin (OT) is under investigation as a treatment for ASD, but OT is a large neuropeptide that has difficulty crossing the blood–brain barrier (BBB). TriozanTM is a nanoformulation that can facilitate OT to cross the BBB. Thus, we investigated the impact of maternal postpartum SSRIs and offspring preadolescent OT treatment on adult offspring neuroinflammation, social behavior, and neurogenesis in the hippocampus. Using a model of de novo postpartum depression, corticosterone (CORT) was given in the postpartum to the dam with or without treatment with the SSRI, fluoxetine (FLX) for 21 days postpartum. Offspring were then subsequently treated with either OT, OT + TriozanTM, or vehicle for 10 days prior to adolescence (PD25-34). Maternal FLX decreased hippocampal IL-10 and IL-13 and neurogenesis in both sexes, whereas maternal CORT increased hippocampal IL-13 in both sexes. Maternal CORT treatment shifted the neuroimmune profile towards a more proinflammatory profile in offspring hippocampus, whereas oxytocin, independent of formulation, normalized this profile. OT treatment increased hippocampal neurogenesis in adult males but not in adult females, regardless of maternal treatment. OT treatment increased the time spent with a novel social stimulus animal (social investigation) in both adult male and female offspring, although this effect depended on maternal CORT. These findings underscore that preadolescent exposure to OT can reverse some of the long-lasting effects of postpartum maternal CORT and FLX treatments in the adult offspring. In addition, we found that maternal treatments that reduce (CORT) or increase (FLX) hippocampal inflammation in dams resulted in opposing patterns of hippocampal inflammation in adult offspring.
... Oxytocin may interact with the dopaminergic system during social interactions [81], increasing the individual's intrinsic social motivation [9]. It may dampen the HPA axis [63], reducing the physiological response to stressors, consequently influencing behaviour [61,85]. Finally, based on the social salience theory, the interaction between the oxytocin and the dopaminergic system could enhance the salience of both negative and positive social cues, leading to different behavioural effects of oxytocin, dependant on the context and the stimuli involved [8,75]. ...
... To take this possibility into account, we measured the frequency of the dog's self-directed behaviours (e.g. head shaking, yawning, lips licking), which are thought to be linked to stress/distress [11,12]. Considering oxytocin's alleviating effects on stress [40,63,85], we predicted that oxytocin administration would reduce (compared to placebo) dogs' display of self-directed behaviours, which would hence indicate a decrease in dogs' aversion to gazing cues (in line with [66]). ...
The relationship between dogs and their owners is characterized by an affective and enduring bond. It has been suggested that oxytocin might be the underlying mechanism driving this relationship, however evidence is mixed. In this study we tested whether intranasally administered oxytocin (compared to saline) would influence dogs’ behavioural synchrony and shared attention towards their owners. Each individuals’ pre and post administration oxytocin concentrations (measured in urine) were included in the analyses. Urinary oxytocin concentrations after administrations were positively associated with dogs’ duration of social proximity and looking behaviours towards their owners supporting the role of oxytocin in modulating dogs’ human-directed social behaviours.
... One emerging concept in depression is that disturbances in allosteric receptor-receptor interactions in highly vulnerable 5-HT1A heteroreceptor complexes can contribute to causing depression and become novel targets for the treatment of depression and anxiety [19,32,33]. Moreover, the 5-HT2A and 5-HT2C receptors are steadily receiving more attention as a therapeutic target for mood disorders [34], and both the GHS-R1a OXTRs have also been implicated in anxiety [35,36]. ...
... It is also of importance that these neurochemical results demonstrating strong antagonistic allosteric receptor-receptor interactions induced by the 5-HT2CR protomers in the above complexes can explain the behavioral results obtained [31]. Indeed, it was observed that the brain-penetrating 5-HT2CR antagonist SB 242,084 could significantly enhance oxytocin-induced hypoactivity in rodents [36,71] which does not represent an additive action [31]. In fact, when given alone, the 5-HT2C antagonist increased locomotor activity. ...
Serotonin communication operates mainly in the extracellular space and cerebrospinal fluid (CSF), using volume transmission with serotonin moving from source to target cells (neurons and astroglia) via energy gradients, leading to the diffusion and convection (flow) of serotonin. One emerging concept in depression is that disturbances in the integrative allosteric receptor–receptor interactions in highly vulnerable 5-HT1A heteroreceptor complexes can contribute to causing major depression and become novel targets for the treatment of major depression (MD) and anxiety. For instance, a disruption and/or dysfunction in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal serotonin neuron systems can contribute to the development of MD. It leads inter alia to reduced neuroplasticity and potential atrophy in the raphe-cortical and raphe-striatal 5-HT pathways and in all its forebrain networks. Reduced 5-HT1A auto-receptor function, increased plasticity and trophic activity in the midbrain raphe 5-HT neurons can develop via agonist activation of allosteric receptor–receptor interactions in the 5-HT1A-FGFR1 heterocomplex. Additionally, the inhibitory allosteric receptor–receptor interactions in the 5-HT1AR-5-HT2AR isoreceptor complex therefore likely have a significant role in modulating mood, involving a reduction of postjunctional 5-HT1AR protomer signaling in the forebrain upon activation of the 5-HT2AR protomer. In addition, oxytocin receptors (OXTRs) play a significant and impressive role in modulating social and cognitive related behaviors like bonding and attachment, reward and motivation. Pathological blunting of the OXTR protomers in 5-HT2AR and especially in 5-HT2CR heteroreceptor complexes can contribute to the development of depression and other types of psychiatric diseases involving disturbances in social behaviors. The 5-HTR heterocomplexes are novel targets for the treatment of MD.
... OTR-mediated signalling within the CNS is mainly involved in modulation of complex social and cognitive related behaviours including bonding, attachment and trust, reward and motivation, as well as fear, anxiety and stress-related responses (Jurek and Neumann, 2018;Lee et al., 2009;Meyer-Lindenberg et al., 2011;Neumann and Slattery, 2016;Sobota et al., 2015;van den Burg and Hegoburu, 2020). OT by regulation of endocrine, physiological, and behavioural functions also promotes sedation and hypoactivity (Teng et al., 2013;Tunstall et al., 2019;Uvnäs-moberg, 1994;Uvnäs-Moberg et al., 1994). Over the past few decades, much effort has been put into understanding the complex behavioural effects of the OT neuropeptide (Keech et al., 2018;Meyer-Lindenberg et al., 2011;Song et al., 2016). ...
... Overall, the behavioural analysis revealed an OT-mediated decrease in locomotor activity, similar to what has been reported previously (Carson et al., 2010;Uvnäs-moberg et al., 1992;Uvnäs-Moberg et al., 1994). Due to the subthreshold dose of OT selected, these effects of OT alone were relatively small, allowing us to observe a synergistic effect of the combined drug treatment. ...
The complexity of oxytocin-mediated functions is strongly associated with its modulatory effects on other neurotransmission systems, including the serotonin (5-hydroxytryptamine, 5-HT) system. Signalling between oxytocin (OT) and 5-HT has been demonstrated during neurodevelopment and in the regulation of specific emotion-based behaviours. It is suggested that crosstalk between neurotransmitters is driven by interaction between their specific receptors, particularly the oxytocin receptor (OTR) and the 5-hydroxytryptamine 2C receptor (5-HTR2C), but evidence for this and the downstream signalling consequences that follow are lacking. Considering the overlapping central expression profiles and shared involvement of OTR and 5-HTR2C in certain endocrine functions and behaviours, including eating behaviour, social interaction and locomotor activity, we investigated the existence of functionally active OTR/5-HTR2C heterocomplexes. Here, we demonstrate evidence for a potential physical interaction between OTR and 5-HTR2C in vitro in a cellular expression system using flow cytometry-based FRET (fcFRET). We could recapitulate this finding under endogenous expression levels of both receptors via in silico analysis of single cell transcriptomic data and ex vivo proximity ligation assay (PLA). Next, we show that co-expression of the OTR/5-HTR2C pair resulted in a significant depletion of OTR-mediated Gαq-signalling and significant changes in receptor trafficking. Of note, attenuation of OTR-mediated downstream signalling was restored following pharmacological blockade of the 5-HTR2C. Finally, we demonstrated a functional relevance of this novel heterocomplex, in vivo, as 5-HTR2C antagonism increased OT-mediated hypoactivity in mice. Overall, we provide compelling evidence for the formation of functionally active OTR/5-HTR2C heterocomplexes, adding another level of complexity to OTR and 5-HTR2C signalling functionality.
This article is part of the special issue on Neuropeptides.
... Administration of oxytocin influences spontaneous motor behaviour in rats in a complex way. A single dose of oxytocin increases (low dose) or decreases (high dose) spontaneous motor activity in rats [51]. Repeated administration of oxytocin (1 mg/kg s.c. ...
... The parameters recorded are defined as follows: Locomotor activity (all horizontal activity registered by photocells), Forward locomotion (horizontal activity, when the animal is moving in the same direction), and Peripheral activity (horizontal activity within 25 mm from the wall) [51]. ...
Oxytocin is a nonapeptide consisting of a cyclic six amino-acid structure and a tail of three amino acids. It was originally known for its ability to induce milk ejection and to stimulate uterine contractions. More recently, oxytocin has been shown to stimulate social behaviors, and exert pain-relieving, anti-stress/anti-inflammatory and restorative effects.
We hypothesize that oxytocin is a principal hormone that, in part, exerts its effects after degradation to active fragments with more specific effect profiles.
Experimental findings on rats show that administered oxytocin exerts biphasic effects. For example, after an initial increase in pain threshold, a second more long-lasting increase follows. Blood pressure and cortisol levels initially increase and then reverse into a long-lasting decrease in blood pressure and cortisol. Whereas the initial effects are, the second-phase effects are not blocked by an oxytocin antagonist, but by an opioid mu-antagonist and by an alpha 2-adrenoreceptor antagonist, respectively, suggesting that other receptors are involved. Repeated administration of oxytocin induces multiple anti-stress effects, which are mediated by alpha 2-adrenoreceptors. Repeated administration of linear oxytocin and linear oxytocin fragments with a retained C-terminal reduce spontaneous motor activity, a sedative or anti-stress effect, suggesting that alpha 2-adrenoreceptors have been activated. In contrast, linear mid-fragments stimulate motor activity.
Low-intensity stimulation of cutaneous nerves in rats, as well as breastfeeding and skin-to-skin contact between mothers and babies, trigger immediate anti-stress effects. Some of these effects are likely caused by open ring/linear C-terminal fragments activating alpha 2-adrenoreceptors.
Oxytocin fragments may be pre-formed and released in the brain or created by metabolic conversion of the principal hormone oxytocin in the central nervous system. Oxytocin and its fragments may also be released from peripheral sites, such as peripheral nerves, the gastrointestinal tract, and blood vessels in response to decreased sympathetic or increased parasympathetic nervous tone. Smaller fragments of oxytocin produced in the periphery may easily pass the blood-brain barrier to induce effects in the brain.
In conclusion, oxytocin is linked to many different, sometimes opposite effects. The intact cyclic molecule may act to initiate social interaction and associated psychophysiological effects, whereas linear oxytocin and C-terminal fragments may induce relaxation and anti-stress effects following social interaction. In this way, the principal hormone oxytocin and its fragments may take part in a behavioral sequence, ranging from approach and interaction to calm and relaxation. Linear fragments, with an exposed cysteine-residue, may exert anti-inflammatory and antioxidant effects and thereby contribute to the health-promoting effects of oxytocin.
... Body weight and developmental milestone monitoring The SD rats underwent daily weighing for the first 8 days after birth (P0-P7), allowing for regular and frequent assessments to closely monitor for potential adverse effects of OXT administration. Although major adverse reactions of OXT were not expected, there were potential risks of bleeding from the subcutaneous injection as well as overall sedation secondary to OXT toxicity (Uvnäs-Moberg et al., 1994). From P7 onward, rats were weighed every other day until P21, followed by weekly body weight monitoring until P42 (6 weeks) of age. ...
Background
Pediatric dysphagia is a prominent feature of neurodevelopmental disorders, such as Prader–Willi syndrome (PWS). Dysphagia increases the risk of malnutrition, aspiration, and subsequent respiratory infections, highlighting the importance of improving the understanding and management of dysphagia.
Aim
The present study investigated the potential role of oxytocin (OXT) in advancing feeding and swallowing behaviors in postnatal day 0 (P0) to P42 (6-week-old) rats, with potential therapeutic implications for PWS. We hypothesized that OXT administered subcutaneously in Sprague Dawley rats within 12 to 24 hours of birth would accelerate the maturation of feeding and swallowing behaviors compared to naïve and saline-treated controls.
Methods
Importantly, the videofluoroscopic swallow study (VFSS) protocol was successfully adapted to evaluate rats as young as P21, broadening the application of this protocol beyond the previous limitation of 6-week-old rats. Using an adapted VFSS protocol for juvenile (P21–P35) and peripubertal (P36–P42) rats, feeding and swallowing maturation was objectively characterized using custom JawTrack™ software. Protocol adaptations included the refinement of oral contrast formulations for liquid and solid foods and the optimization of fluoroscope settings and equipment. Body weight and developmental milestones (e.g., crawling, walking, self-feeding) were also recorded.
Results
OXT modulated specific feeding behaviors in juvenile rats (i.e., lick rate and inter-lick interval). However, OXT did not significantly accelerate the attainment of developmental milestones in rats, and the selective effects on feeding behaviors were not observed to extend into the peripubertal stage.
Conclusion
The present study establishes a useful methodology for future research using our enhanced VFSS protocol. In light of these results, future research is well-positioned to expand our understanding of the potential of OXT to treat dysphagia in neurodevelopmental disorders.
... Oxytocin is well known to mediate anti-stress effects (for example, by decreasing cortisol levels and blood pressure). In rats, oxytocin can induce both anxiolyticlike and sedative effects depending on dose and route of administration but also depending on the stage of the estrous cycle [121,122]. The effects of oxytocin administered postnatally to pigs and rats may even induce lifelong behavioral changes [123][124][125]. ...
The hypothalamic neuropeptide and hormone oxytocin are of fundamental importance for maternal, social, and sexual behavior. Deviations in oxytocin levels have also been associated with anxiety, autism spectrum disorders (ASD), depression, ADHD (attention deficit hyperactivity disorder), and schizophrenia. Both oxytocin and dopamine are often considered reward- and feel-good hormones, and dopamine is associated with the above-mentioned behaviors and, and dopamine is also associated with the above-mentioned behaviors and disorders. Although being structurally totally different, oxytocin, a peptide, and dopamine, a monoamine, they have a number of similar effects. They are synthesized both in the brain and in the periphery, and they affect each other’s release and receptors. In addition, oxytocin and dopamine are released in response to, for example, social interaction, sex, feeding, and massage. This review discusses interactions between oxytocin and dopamine with a specific focus on behavioral effects and possible roles of oxytocin and dopamine in various mental disorders and functional diversities.
... 20 Its release also impacts the immune system, increasing the threshold for pain, and providing an anti-inflammatory and anxiolytic effect. 21 Furthermore, the parasympathetic nervous system functioning is improved as well as the endocrine system wherein the gastrointestinal tract and digestive function are benefitted leading to growth and restoration. 22 It is distributed throughout the nervous system, impacting gastrointestinal, socio-sexual and cardiovascular health. ...
Animal-assisted therapy is a new and upcoming form of therapy that has shown multifarious benefits to participants. It is a goal-oriented therapeutic process with the incorporation of a qualified therapy animal in the therapeutic activities and conversations. This paper explores these benefits from a psychoneuroimmunological lens, wherein the interplay of and impact on an individual's psychological, neurological and immune systems are discussed. Positive physical interaction with therapy animals reduces undesirable symptoms and ailments such as stress, anxiety, depressive symptoms, aggressive tendencies, harmful behaviours, cardiovascular issues and unhealthy tendencies amongst others. It further promotes a healthier lifestyle, promoting quality of life, better heart health, cognitive functioning and overall well-being. The biological basis of these benefits is discussed.
... As discussed above, in relation to the effects of oxytocin on metabolism and weight, likewise, oxytocin seems to have dual effects also in some aspects of behavior. In rats, oxytocin can induce both anxiolytic-like and sedative effects depending on dose and the route of administration but also depending on the stage of the estrous cycle [37,62], and oxytocin administered postnatally to pigs and rats induces lifelong behavioral changes [47,49,63]. ...
Prader–Willi Syndrome (PWS) is a rare genetic disorder typically characterized by decreased social interaction, hyperphagia, poor behavioral control and temper tantrums, together with a high risk of morbid obesity unless food intake is controlled. The genetic defects that cause PWS include paternal 15q deletion (estimated in 60% of cases), chromosome 15 maternal uniparental disomy (UPD) (estimated in 35% of cases) and imprinting defects and translocations. Several studies indicate an oxytocin deficiency in PWS. Oxytocin is a hypothalamic nonapeptide with receptors located in the brain and in various other tissues in the body. It acts as a neuropeptide in several brain areas of great importance for behavioral and metabolic effects, as well as a neurohypophyseal hormone released into the circulation. Oxytocin in both rats and humans has strong and long-lasting behavioral and metabolic effects. Thus, an oxytocin deficiency might be involved in several of the behavioral and metabolic symptoms characterizing PWS. Treatment with oxytocin has, in some studies, shown improvement in psycho-social behavior and hyperphagia in individuals with PWS. This review focus on the behavioral and metabolic effects of oxytocin, the symptoms of a potential oxytocin deficiency in PWS and the effects of oxytocin treatment.
... The central administration of oxytocin has been shown to improve preclinical stress-related measures, such as anxiety-like responses, depression-like responses, alcohol drinking, and stressinduced corticosterone levels [4][5][6][7][8][9][10][11][12]. Oxytocin, opioid peptides (e.g., β−endorphin and leu-and met-enkephalin) [13,14], and their class A G-protein coupled oxytocin and μ−opioid receptors are key components of the neurocircuitry of the hypothalamus and the extended amygdala, i.e., brain regions that mediate stress and emotion regulation [15,16]. ...
Mood and anxiety disorders are leading causes of disability worldwide and are major contributors to the global burden of diseases. Neuropeptides, such as oxytocin and opioid peptides, are important for emotion regulation. Previous studies have demonstrated that oxytocin reduced depression- and anxiety-like behavior in male and female mice, and opioid receptor activation reduced depression-like behavior. However, it remains unclear whether the endogenous opioid system interacts with the oxytocin system to facilitate emotion regulation in male and female mice. We hypothesized that opioid receptor blockade would inhibit the anxiolytic- and antidepressant-like effects of oxytocin. In this study, we systemically administered naloxone, a preferential μ−opioid receptor antagonist, and then intracerebroventricularly administered oxytocin. We then tested mice on the elevated zero maze and the tail suspension tests, respective tests of anxiety- and depression-like behavior. Contrary to our initial hypothesis, naloxone potentiated the anxiolytic-like, but not the antidepressant-like, effect of oxytocin. Using a selective μ−opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, and a selective κ−opioid receptor antagonist, norbinaltorphimine, we demonstrate that μ−opioid receptor blockade potentiated the anxiolytic-like effect of oxytocin, whereas κ−opioid receptor blockade inhibited the oxytocin-induced anxiolytic-like effects. The present results suggest that endogenous opioids can regulate the oxytocin system to modulate anxiety-like behavior. Potential clinical implications of these findings are discussed.
... pressure (BP) and stress responses are well documented in animal models but less well established in humans (Carter, 1998;Carter, Devries, & Getz, 1995;Insel, 1997;Keverne & Kendrick, 1997;Pedersen, Ascher, Monroe, & Prange, 1982;Uvnas-Moberg, 1998a, 1998b. In rats, administration of oxytocin or natural oxytocin released by stroking leads to decreases in both BP and cortisol levels and to diminished distress behavior (Agren, Lundeberg, Uvnas-Moberg, & Sato, 1995;Uvnas-Moberg, Ahlenius, Hillegaart, & Alster, 1994). After 5 days of daily oxytocin injections to rats, BP reductions of 10 to 20 mm Hg persist for 1 to several weeks, even though the plasma half-life of oxytocin is minutes (Uvnas-Moberg, 1998a, 1998bPetersson, Alster, Lundeberg, & Uvnas-Moberg, 1996a, 1996b. ...
The neuropeptide oxytocin (OT) enhances maternal behavior and decreases blood pressure (BP) and stress responses in animals. Thus, the relationship of OT responsivity to BP in 14 breast- and 11 bottle-feeding mothers of infants was examined. Laboratory BP was assessed during baseline, speech preparation, active speech, and recovery on 2 days, 1 in which baseline and speech were separated by 10 min of baby holding and the other by no baby contact. Systolic BP reactivity to speech was lower after baby contact. Plasma OT change from baseline to speech after baby contact defined OT increase, minimal OT change, and OT decrease groups. OT increase mothers were primarily breast-feeders, and they had lower BP throughout both stress sessions and after baby feeding at home than OT decrease mothers, who also had greater BP reactivity to preparation and recovery. These results suggest that oxytocin has antistress and BP-lowering effects in humans.
... The decrease in activity is similar to results in studies with mammals. For example, reports of OTlike sedative effects were found in male Sprague-Dawley rats, with low doses of subcutaneous OT decreasing locomotor activity and higher doses showing sedative effects [76]. Likewise, intraperitoneal OT reduced locomotor activity of adult male rats [3] and mice [48]. ...
The oxytocin family of neuropeptides is implicated in the regulation of sociality across vertebrates. Non-mammalian homologs of oxytocin, such as isotocin in fish and mesotocin in amphibians, reptiles and birds, all play crucial roles modulating social and reproductive behavior. In this study, we exogenously manipulated the mesotocinergic system in a highly social bird, the common waxbill Estrild astrild, and tested the effects on affiliative and aggressive behavior by performing tests of competition over food. Birds treated with mesotocin showed a sedative state, decreasing almost all the behaviors we studied (movement, feeding, allopreening), while birds treated with an oxytocin antagonist showed a decrease only in social behaviors (aggressions and allopreening). We also found two sex-specific effects: mesotocin reduced allopreening more in males than females, and the oxytocin antagonist reduced aggressiveness only in females. Our results suggest sex-specific effects in the modulation of affiliative and aggressive behaviors via mesotocinergic pathways.
... In addition to its well-known function in childbirth and lactation, OXT can modulate a variety of responses to social and emotional challenges at different life stages in humans [144,145] and rodents [142,[146][147][148]. For example, there is evidence showing that OXT attenuates sustained contextual fear, anxiety-like behavior and the HPA axis activity during stress [149][150][151]. On the other hand, OXT can sometimes produce opposite two-way behavioral reactions, including anxiogenic or anxiolytic behaviors and increased or decreased stress response [152]. ...
Scientists have systematically investigated the hereditary bases of behaviors since the 19th century, moved by either evolutionary questions or clinically-motivated purposes. The pioneer studies on genetic selection of laboratory animals had already indicated, one hundred years ago, the immense complexity of analyzing behaviors that were influenced by a large number of small-effect genes and an incalculable amount of environmental factors. Merging Mendelian, quantitative and molecular approaches in the 1990s made it possible to map specific rodent behaviors to known chromosome regions. From that point on, Quantitative Trait Locus (QTL) analyses coupled with behavioral and molecular techniques, which involved in vivo isolation of relevant blocks of genes, opened new avenues for gene mapping and characterization. This review aims at examining the QTL strategy applied to the behavioral study of emotionality, with a focus on the laboratory rat. We discuss challenges, advances and limitations of the search for Quantitative Trait Genes (QTG) playing a role in the regulation of emotionality. For the past 25 years, we have marched the long journey from emotionality-related behaviors to genes. In this context, our experiences are used to illustrate why and how one should move forward in the molecular understanding of complex psychiatric illnesses. The promises of exploring genetic links between immunological and emotional responses are also discussed. New strategies based on humans, rodents and other animals (such as zebrafish) are also acknowledged, as they are likely to allow substantial progress to be made in the near future.
... This led to a change in the sleep pattern, by decreasing REM sleep and increasing neural activity, with high-frequency waves being recorded on the electroencephalogram. On the other hand, the administration of high doses of oxytocin determined decreased locomotor activity in experimental animals. When oxytocin was administered in relatively low doses, the researchers also observed an anxiolytic effect on animal subjects [110]. The studies report those outcomes dependent on the presence or absence of stress, confirming the connection between the oxytocin system and stress while also suggesting a possible involvement of oxytocin in sleep changes found in depression. ...
Is a cyclic neuropeptide produced primarily in the hypothalamus and plays an important neuromodulatory role for other neurotransmitter systems, with an impact on behavior, response to danger, stress, and complex social interactions, such as pair bonding and child care. This narrative expert review examines the literature on oxytocin as a brain hormone. We focused on oxytocin structure, distribution, genetics, and the oxytocin receptor system, as well as the relationship of oxytocin with other neurotransmitters and the resulting impacts on the main psychiatric disorders. Oxytocin levels have been correlated over time with mental illness, with numerous studies focusing on oxytocin and the pathophysiology of the main psychiatric disorders, such as autism, schizophrenia, personality disorders, mood, and eating disorders. We highlight the role oxytocin plays in improving symptoms such as anxiety, depression, and social behavior, as the literature suggests. Risk factors and causes for psychiatric disorders range from genetic to environmental and social factors. Oxytocin could impact the latter, being linked with other neurotransmitter systems that are responsible for integrating different situations during the development phases of individuals. Also, these systems have an important role in how the body responds to stressors or bonding with others, helping with the creation of social support groups that could speed up recovery in many situations. Oxytocin has the potential to become a key therapeutic agent for future treatment and prevention strategies concerning the main psychiatric disorders.
... As with all studies involving OT, one may speculate that-to some extent-hypophagia may be exacerbated by a mild sedating effect of the drug (for example, see [39]). It should be noted, however, that the 0.1 mg/kg OT dose that was used in combination with NTX here is subthreshold to suppress feeding alone (and well below doses widely administered in feeding studies thus far [15]). ...
A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.
... The OT system is implicated in several psychiatric disorders, including anxiety and depression, which are intricately connected to the stress response (Neumann and Landgraf, 2012). High peripheral doses of OT have been shown to suppress anxiety (Uvnäs-Moberg et al., 1994). Depressive-and anxiety-like behavior has been observed in mice subjected to OT via injections into the amygdala. ...
Neuropeptides being regulators of the hypothalamus-pituitary-adrenal (HPA) axis activity, also affect the function of the hypothalamus-pituitary-gonadal (HPG) axis by regulating gonadotrophin-releasing hormone (GnRH) secretion from hypothalamic neurons. Here, we review the available data on how neuropeptides affect HPG axis activity directly or indirectly via their influence on the HPA axis. The putative role of neuropeptides in stress-induced infertility, such as polycystic ovary syndrome, is also described. This review discusses both well-known neuropeptides (i.e., kisspeptin, Kp; oxytocin, OT; arginine-vasopressin, AVP) and more recently discovered peptides (i.e., relaxin-3, RLN-3; nesfatin-1, NEFA; phoenixin, PNX; spexin, SPX). For the first time, we present an up-to-date review of all published data regarding interactions between the aforementioned neuropeptide systems. The reviewed literature suggest new pathophysiological mechanisms leading to fertility disturbances that are induced by stress.
... Oxytocin, sometimes known as the 'cuddle hormone' or the 'love hormone' , can be released in both humans and non-human animals after a positive physical contact such as close physical proximity, snuggling up to each other and touching each other. A higher release of this chemical might help reduce depressive and anxiety-related symptoms (Uvnäs-Moberg et al., 1994). ...
Although animal-assisted interventions (AAIs) share specific characteristics, their differences can be quite significant (Lajoie, 2003). Most research on AAIs focuses on the human side (Muñoz Lasa et al., 2011). The autonomy and well-being of the animals involved are seldom studied, as well as the possible values of conflict between humans and animals (Glenk, 2017). The COVID-19 pandemic that gripped the world starting in 2019–2020, greatly affected human-animal interaction projects, such as animal-assisted interventions (Kumar et al., 2020). To control the spread of the SARS-CoV-2 virus, several (inter)national organisations, came up with new safety protocols. We focus on scientific insights and anecdotal observations, as well as the ethical implications of the COVID-19 safety protocols on AAIs in Belgium and Italy. The paper aims to give the reader an insight into the complexity of AAIs and its future relevance for developing protocols to handle the current and maybe future pandemics.
https://brill.com/view/journals/jaae/aop/article-10.1163-25889567-BJA10019/article-10.1163-25889567-BJA10019.xml
... For example, OXT demonstrated significant cytoprotective effects (Alizadeh et al. 2012;Das and Sarkar 2012) and improved mitochondrial function which may result in improved oxidative state (Gravina et al. 2011;Griffiths and Rutter 2009). OXT is not only a potent treatment alleviating anxiety and depression (Arletti and Bertolini 1987;Uvnas-Moberg et al. 1994;Yoshida et al. 2009), but also it increases the resilience and reduces the susceptibility to develop anxiety and depression with known and unknown mechanisms (Le Dorze et al. 2020;Sharma et al. 2020). It is also plausible that reduced level of OXT makes the brain susceptible to anxiety and depression, rather than directly causing them. ...
Huntington disease (HD) is a progressive neurological disorder with dominant motor symptoms. It also has psychiatric manifestations, like anxiety and depression, that can emerge themselves before motor symptoms and impose a major burden on patients. Oxytocin (OXT) is a newly emerged treatment for disorders like autism and schizophrenia and recently is using to alleviate depression and anxiety. In the current study, we investigated the behavioral and molecular effects of OXT on the development of anxiety and depression in 3-nitropropionic acid (3-NP)-induced model of HD. Anxiety- and depression-like behaviors as well as the levels of oxytocin receptor (OXTR), metabotropic glutamate receptor (mGluR) 2, mGluR5, and glutathione (GSH) were measured in striatum, hippocampus, prefrontal cortex, and amygdala. Also, we questioned if sex had any modulatory effect. We found that 3-NP increased anxiety and depression compared to controls. It also reduced the levels of OXTR and mGluR2, increased mGluR5, and reduced GSH in studied brain regions. Pretreatment with OXT before the injection of 3-NP ameliorated anxiety and depression. Additionally, it protected the brain from developing low levels of OXTR, mGluR2, and GSH and high levels of mGluR5 in studied regions. The protective effects of OXT were similar between male and female animals. These data suggest that OXTR, mGluR2, mGluR5, and GSH may contribute to psychiatric manifestations of HD. In addition, pretreatment with OXT could prevent the mood changes in male and female rats.
... In rats, gentle stroking was found to decrease arterial blood pressure [29]. Studies in dogs [30] have shown that gentle petting increases oxytocin release, which has various benefits on overall health [31][32][33][34]. ...
Simple Summary
Stress in cats residing in a shelter environment is a significant contributor to the development of upper respiratory disease (URD). Previous studies have shown that positive interactions can reduce stress and enhance the immune system. However, little is known on how the frequency and duration of daily handling affects a cat’s likelihood of developing URD. The goal of this study was to record the daily frequency and duration of handling of clinically healthy cats that were relinquished at a closed admission shelter and determine if these parameters were associated with a statistically significant increased risk of developing URD. While no parameters were statistically significantly associated with an increased hazard of developing URD, we found that cats that did not develop URD were handled more frequently than cats that did develop URD. Our results suggest that increased frequency and duration of handling does not appear to increase the risk of URD signs and may reduce the incidence of URD development. These results are important for the shelter community in developing handling and hygiene protocols for shelter cats.
Abstract
Reducing stress is important to maintaining the health of shelter cats and decreasing the risk of upper respiratory disease (URD). The aim of this study was to determine if the frequency and/or duration of daily routine handling of shelter cats affects the likelihood of URD development. At a closed admission shelter, each cat free of URD on intake was given a cage card for recording handling data. These data included: date and times when the cat was handled, duration of handling, if and when the cat developed signs of URD, and the handler identity. Cox regression was used to determine the relationship between these factors and URD development. We found cats that did not develop URD were handled significantly more than cats that did (1.1 times per day vs. 0.7 times per day, p < 0.001). Increased frequency of handling had a borderline significant effect on the hazard of developing URD (HR 0.37; CI: 0.13–1.1; p = 0.066). No other parameters were significantly associated with the development of URD; however, small sample size may be responsible for this finding. A larger study is needed to elucidate the relationship between handling and URD development.
... Also, 100 mg/kg SM EtOH did not show significant sedative effects but only have anxiolytic effect. The reasonable explanation is that anxiolytic effects and sedative effects are dependent to the dose (Uvnäs-Moberg et al., 1994). This observation is consistent with the guidelines of tradition Chinese medicine prescription, which mentions that nourishing the heart and tranquilizing the mind requires a low dose of Danshen, whereas sedation requires a high dose (Fang et al., 2010). ...
Ethnopharmacological relevance
Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has demonstrated in modern studies for its pharmacological activities in treatments of CNS disorders like insomnia, dysphoria. However, its application on anxiolytic effect from the ethanol extract of Salvia miltiorrhiza Bunge (SMEtOH) has not yet been reported.
Materials and methods
This study investigated the anxiolytic effect of the SMEtOH using the elevated plus-maze test (EPM) and the hole-board test (HBT) with diazepam and buspirone as positive controls. Also, the spontaneous locomotor activity of mice had been investigated in the open field. Further, we have illustrated the anxiolytic mechanisms of SMEtOH with its influencing upon GABAergic and/or serotonergic nervous systems via a method that SMEtOH was co-administered with flumazenil, a benzodiazepine (BZD) antagonist, or a drug (WAY-100635), a selective 5HT1A receptor antagonist.
Results
In hole-board test, results presented that SMEtOH increased head-dip counts and duration time. On the other hand, a decrease in spontaneous locomotor activity was observed. In the EPM test, SMEtOH increased the percentage of open-arm entries and the percentage of time spent in open arms. However, when SMEtOH co-administered with flumazenil or WAY-100635, the anxiolytic effect of SMEtOH was significantly counteracted.
Conclusion
From these results, we can conclude that the anxiolytic mechanism of SMEtOH is exerted through an activation of the BZD and 5HT1A receptors.
... Although, the mechanism of Impairing hypothesis is not fully understood, several studies have indicated that oxytocin decreased the initial storage of information and the amount of storage [24]. In this line, studies also have suggested that reducing the speed and performance in tasks after administration of oxytocin was due to its sedative effects [25,26]. Complementarily, it was proposed that oxytocin is an effective factor in these modifications by reducing the cortisol levels and anxiety in response to physical stress [27]. ...
Studies have indicated that oxytocin has an influence on cognitive functions such as attention, memory and emotional regulation, particularly in the context of social and communicative behavior. There is a growing interest in the use of oxytocin as a treatment for memory-related psychological disorders and social cognitive disorders. The ease of access to the brain intranasally, numerous positive evidences and widely advertised as a wonder drug, foster this interest. However, recent studies also have shown that the effect of oxytocin could varied, even leading to reverse results. The factors that lead to the effects of oxytocin and its underlying processes on such variables are still uncertain. The inconsistent evidence of general oxytocin effects on memory and neuropsychological conditions is an important issue in considering oxytocin as an adjunct therapy. Therefore, understanding the effects of oxytocin, within various emotional and social context, is important before oxytocin could be efficiently used for improving learning and communication impairment or managing neuropsychological disorders. Here, we intend to review various theories regarding the effect of oxytocin on memory, accompanied by its mechanisms which are proposed in human and animal experiments. Based on evidence from these studies, we explore the potentials and limitations of oxytocin’s pharmacotherapeutic applications as a treatment to improve neuropsychological disorders.
... This helps reduce depressive and anxiety-related symptoms, improves memory, perception of oneself and social skills. It also impacts the immune system, providing an increased pain threshold, and anti-inflammatory effects, that is, it reduces inflammation or swelling in the body (10). Oxytocin has widespread pathways in the brain and hence regulates a variety of functions and release of other neurotransmitters too. ...
Companion animals and pets can be helpful during the novel coronavirus-19 pandemic. Interactions with them and positive physical contact lead to a variety of physiological and psychological benefits. It also releases biochemicals which can further boost the immune system and enhance health and well-being. This perspective discusses the benefits of these interactions, the modes of interactions and the activities that can be used. It also highlights the individuals that should avoid this approach and the status of the animal’s health before engaging with them.
... The peripheral administration of OXT to HFD-fed mice did not affect the duration of time spent in the center in our open field tests. Previous studies however reported that wild-type rats fed with normal chaw showed reduced anxiety behavior when subjected to the open field test following the peripheral administration of OXT (66). In our study, anxiety behavior was not reduced in mice, suggesting that the pathology induced by a HFD and the physiological effects of OXT administration may not always be the same in rats and mice. ...
Excessive intake of fat is a major risk factor for lifestyle-related diseases such as heart disease and also affects brain function such as object recognition memory, social recognition, anxiety behavior, and depression-like behavior. Although oxytocin (OXT) has been reported to improve object recognition, social recognition, anxiety behavior, and depression-like behavior in specific conditions, previous studies did not explore the impact of OXT in high-fat diet (HFD)-fed mice. Furthermore, it remains unclear whether intake of HFD affects OXT/oxytocin receptor (OXTR) in the brain. Here, we demonstrated that peripheral OXT administration improves not only social recognition but also object recognition and depressive-like behavior in HFD-fed mice. In contrast, peripheral OXT administration to HFD-fed male mice increased fear and anxiety-related behavior. In addition, we observed that intake of HFD decreased OXTR and c-fos mRNA expression in the hippocampus, specifically. Furthermore, peripheral OXT administration increased OXT mRNA expression in the hypothalamus. Altogether, these findings suggest that OXT has the potential to improve various recognition memory processes via peripheral administration but also has side effects that increase fear-related behavior in males.
... Intracerebral oxytocin has anxiolytic effects by dampening the responsiveness of the HPA-axis. This has been shown in animal (Neumann, Krömer, Toschi, & Ebner, 2000;Uvnäs-Moberg, Ahlenius, Hillegaart, & Alster, 1994;Windle, Shanks, Lightman, & Ingram, 1997) as well as human research (Heinrichs, Baumgartner, Kirschbaum, & Ehlert, 2003;Koch et al., 2016). Further, evidence from neuroimaging studies suggests that this effect is mediated by a downregulation of amygdala activity (Baumgartner, Heinrichs, Vonlanthen, Fischbacher, & Fehr, 2008;Domes, Heinrichs, Gläscher, et al., 2007;Kanat, Heinrichs, Mader, van Elst, & Domes, 2015;Petrovic, Kalisch, Singer, & Dolan, 2008). ...
... In addition, oxytocin antagonists, centrally infused, yield 9 increased activation of the HPA axis in mice [5]. Although central oxytocin administration has 10 an inhibitory effect on the HPA axis in animals, peripheral administration of oxytocin also 11 attenuates the HPA axis in mice [8,9] and humans [10]. Conversely oxytocin and cortisol may be 12 interdependent at the onset of a novel stressor whereby oxytocin may potentiate the HPA axis 13 response but overtime has been shown to have an attenuating effect on the HPA axis [11]. ...
Changes in the physiological, psychological, and behavioral manifestations of stress have been observed in association with increases in circulating oxytocin (OXT). Providing OXT intranasally has been shown to attenuate stressor-induced hypothalamo-pituitary-adrenal (HPA) axis activation in humans and rodents; however, anxiolytic effects may be context and species specific. The present study aimed to investigate the effect of intranasal OXT supplementation on stressor-induced activation of the HPA axis in beef cattle. We hypothesized that OXT would attenuate activation of the HPA axis, ultimately decreasing plasma cortisol and adrenocorticotropic hormone (ACTH). Twenty-eight Bos taurus heifers were blocked by bodyweight and randomly allocated to one of four treatment groups, in a 2 × 2 factorial arrangement: (1) saline, isolated, standing, and unrestrained (S-isolation stress [IS], 0.015 mL/kg BW 0.9% isotonic saline, n = 7); (2) saline, isolated, and restrained (S-restraint and isolation stress [RIS]; 0.015 mL/kg BW 0.9% isotonic saline; n = 7); (3) OXT, IS (OXT-IS, 0.3 IU/kg BW oxytocin; n = 7); and (4) OXT and RIS (OXT-RIS, 0.3 IU/kg BW oxytocin; n = 7). Oxytocin and saline were administered intranasally. Intranasal treatments were given followed by a waiting time of 30 min when each of the stress treatments was applied for 2 h. Blood samples were collected via jugular catheters directly after stressor application and every 10 min thereafter, for 2 h. Cortisol concentrations increased over time in animals exposed to RIS (P < 0.01) and decreased over time in animals exposed to IS (P < 0.01). Concentrations of ACTH decreased over time for the IS-treated heifers but remained elevated for the RIS-treated heifers (P < 0.01). Under the conditions of the present study, OXT treatment did not affect measured indicators of HPA axis activation. A treatment × time interaction (P < 0.01) was detected for OXT, such that OXT heifers exhibited greater initial OXT concentrations followed by a decline; saline-treated heifers had consistently stable oxytocin concentrations. The RIS-treated heifers increased their glucose (P < 0.01) and lactate (P < 0.01) concentrations throughout the application of the stressors compared with the IS-treated heifers. Overall, restraint stress increased cortisol and oxytocin in B taurus heifers compared with heifers subjected only to isolation. Finding a more intermediate stress model may better allow for detection of the effects of oxytocin on the stress response.
This article summarizes my scientific work and describes some personal experiences during this period. After my basal medical training (MD) (1971), I obtained a PhD in pharmacology (1976) and ended up as a professor of Physiology.
My initial studies were within the field of gastroenterology. I showed that the gastrointestinal hormone gastrin, which stimulates HCL secretion in the stomach, was released in response to stimulation of the vagal nerve. Later I showed that the entire endocrine system of the gastrointestinal (GI) tract that promotes digestion and anabolic metabolism and growth was under vagal nerve control. I also showed that activation of the vagal nerve inhibits the function of the inhibitory substance somatostatin.
10 years later, after some big changes in my personal life, my research focus changed. I became interested in female physiology, particularly the role of oxytocin. In addition, I became aware of the situation of female scientists and started to work with questions regarding equality between women and men.
I gathered a group of interested female medical students and midwives around me. We demonstrated that breastfeeding and touch (e.g., between mother and baby), via stimulation of sensory nerves in the skin, activated the endocrine system of the GI tract and, thereby, anabolic processes and growth. The effects were exerted via a vagal mechanism and involved activation of parvocellular oxytocinergic neurons from the paraventricular nucleus (PVN). We also showed that the gastrointestinal hormone cholecystokinin stimulated the release of oxytocin in a calorie-dependent way via an afferent vagal mechanism.
In summary, there is a bidirectional, vagally mediated connection between the endocrine system of the GI tract and the oxytocin producing neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus.1. Oxytocinergic neurons from the PVN enhances the activity of the endocrine system of the GI tract and thereby growth and regeneration. The effect is exerted via efferent vagal fibers which inhibit the release of somatostatin. 2. Food in the duodenum triggers a release of cholecystokinin (CCK), which via a vagal afferent mechanism stimulates the release and function of oxytocin. This mechanism is not activated in the absence of food intake.
Administration of oxytocin induces a multitude of actions, i.e., anxiolytic and sedative effects, increased pain threshold, lowering of cortisol and blood pressure and an increased activity of the endocrine system of the GI tract. Repeated administration of oxytocin may induce long-term effects and “secondary” mechanisms such as an increased activity of alpha-2- adrenoceptors are involved.
Oxytocin released by suckling during breastfeeding or by touch during social interaction will induce a similar effect spectrum. Activation of the parvocellular neurons will stimulate some aspects of social behavior, induce calm and well-being, and decrease levels of fear, stress, and pain. In addition, vagal functions and the activity of the endocrine system of the GI tract will be stimulated. Together, these effects are consistent with the oxytocin-mediated calm and connection response and, in a long-term perspective, with the promotion of well-being and health.
A second period of professional difficulties occurred in the late 1990s. I moved to the Swedish University of Agriculture, where I started to investigate the role of oxytocin in interactions between humans and pets, as this type of interaction had been shown to promote health. I continued to study the role of oxytocin in female reproduction, in particular, the role of oxytocin during labor and birth and in the peripartum period. In addition, I started to write books about different aspects of oxytocin.
I also wanted to establish a role for oxytocin in the treatment of vaginal atrophy. Several clinical studies show that local intravaginal application of oxytocin in women with vaginal atrophy increases the regeneration of vaginal mucosal cells and function.
Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 μg), kisspeptin + astressin 2B (1 μg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.
Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities.
Oxytocin (OXT) is a neuropeptide that regulates memory, emotion, stress response, and behavior in the brain. In our previous study with cattle, we demonstrated the anti-stress effect of intracerebroventricularly administered OXT on the central nervous system. However, it is important to investigate the effects of this peptide after intranasal administration, as it offers convenience and non-invasiveness for practical use. Therefore, this study investigated the effects of intranasal OXT on the behavior and autonomic nervous system of Holstein steers. The experiment followed a within-subjects design, including a total of six steers. Each steer received intranasal administration of either 1 mL of saline (SAL), 100 µg OXT (OXT100), or 200 µg OXT (OXT200). However, due to some issues, the sample size for the OXT200 group was reduced to five. After these treatments, we conducted electrocardiography recordings to analyze heart rate variability (HRV) and also made behavioral observations for 90 min. OXT200 tended to increase the time spent ruminating while lying down (Steel’s multiple comparison test; P=0.053). In contrast, OXT treatment did not affect HRV indices. In conclusion, the current OXT dosage did not significantly affects behavior or the autonomic nervous system. However, the observed tendency to increase rumination may suggest a central effect of OXT.
The aim of the current review was to assess whether parent-performed infant massage (PPIM) could effectively improve the mental state of parents during the postpartum period. Several international electronic databases were thoroughly searched for relevant articles. Included studies observed the influence of PPIM on the mental state of parents of healthy full-term infants within 18 months postpartum or medically stable preterm infants during hospitalization after birth. Nine studies were included, which observed one or more aspects of parental mental state, including depression, anxiety, parental stress, or general mood state. Characteristics of participants, massage protocols, and outcome measures were heterogenous; hence, results regarding the influence of PPIM on parental mental state were inconsistent. Upon further investigation, 10-minute, home-based PPIM for at least 4 weeks is advisable for maternal depression within 5 months postpartum. Moreover, PPIM in a neonatal intensive care unit is advisable for improving the general mood of mothers of preterm infants. Additional methodologically rigorous studies are needed to provide stronger evidence. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].
Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also experience psychiatric and behavioral changes after long-term use. The AAS-induced effects on the brain seem to depend on the type of steroid used, but the rationale behind the observed effect is still not clear. The present study investigated and compared the impact of nandrolone decanoate and testosterone undecanoate on body weight gain, levels of stress hormones, brain gene expression, and behavioral profiles in the male rat. The behavioral profile was determined using the multivariate concentric squared field test (MCSF-test). Blood plasma and brains were collected for further analysis using ELISA and qPCR. Nandrolone decanoate caused a reduction in body weight gain in comparison with both testosterone undecanoate and control. Rats receiving nandrolone decanoate also demonstrated decreased general activity in the MCSF. In addition, nandrolone decanoate reduced the plasma levels of ACTH in comparison with the control and increased the levels of corticosterone in comparison with testosterone undecanoate. The qPCR analysis revealed brain region-dependent changes in mRNA expression, where the hypothalamus was identified as the region most affected by the AAS. Alterations in neurotransmitter systems and stress hormones may contribute to the changes in behavior detected in the MCSF. In conclusion, both AAS affect the male rat, although, nandrolone decanoate has more pronounced impact on the physiological and the behavioral parameters measured.
Saporin conjugated to oxytocin (OXY-SAP) destroys neurons expressing oxytocinergic receptors. When injected unilaterally in the substantia nigra of male rats, OXY-SAP causes a dose-dependent decrease up to 55% in nigral Tyrosine Hydroxylase (TH)-immunoreactivity compared to control mock peptide BLANK-SAP- and PBS-treated rats or the contralateral substantia nigra. TH decrease was parallel to a dopamine content decrease in the ipsilateral striatum compared to BLANK-SAP- or PBS-treated rats or the contralateral striatum. OXY-SAP-treated rats showed a small but significant increase of locomotor activity 28 days after intranigral injection in the Open field test compared to BLANK-SAP- or PBS-treated rats, in line with an inhibitory role of nigral oxytocin on locomotor activity. OXY-SAP-, but not BLANK-SAP- or PBS-treated rats, also showed marked dose-dependent rotational turning ipsilateral to the injected substantia nigra when challenged with D-amphetamine, but not with apomorphine. Under isoflurane anesthesia OXY-SAP-treated rats showed levels of extracellular dopamine in the dialysate from the ipsilateral striatum only half those of BLANK-SAP- or PBS-treated rats or the contralateral striatum. When treated with D-amphetamine, OXY-SAP_60/120 rats showed increased extracellular dopamine levels in the dialysate from the ipsilateral striatum two third/one third only of those found in BLANK-SAP- or PBS-treated rats or the contralateral striatum, respectively. These results show that OXY-SAP destroys nigrostriatal dopaminergic neurons expressing oxytocin receptors leading to a reduced striatal dopamine function.
The consumption of food products containing the non-caloric sweetener aspartame
has increased since the 80’s, when these products were introduced in the market. Since
then, several pieces of evidence suggest that aspartame may be potentially harmful
to the nervous system, although some controversy on this subject still persists. Some
research suggests an association between aspartame intake and metabolic damage to
the central nervous system (CNS), such as changes in enzyme and neurotransmitter
activities. Considering the possible adverse neuronal actions of aspartame, we consider
it important to study the biological effects of this sweetener on the functional aspects
of the CNS. Objective: To analyze the pertinent literature on important aspects of the
possible neurophysiological alterations associated with aspartame consumption. Methods: We conducted a search for studies, whose strategy was developed for Embase,
Medline, Lilacs and Pubmed databases, according to the descriptors: Aspartame, brain
function and nervous system. We present here a narrative review of the literature over
the period from 1992 to 2012. Conclusion: experimental and clinical studies indicate the
risk of neural adverse reactions, which are associated with the use of aspartame, even
in relatively low doses. This risk might be higher in developing organisms. Because of
such evidence we recommend that the sweetener consumption, if any, should be performed with moderation and caution, under the guidance of a nutritionist or a medical
doctor, in order to avoid aspartame-associated deleterious effects on brain function,
mainly in children.
The hypothalamo-neurohypophysial system (HNS), comprising hypothalamic magnocellular neuroendocrine cells (MNCs) and the neurohypophysis, plays a pivotal role in regulating reproduction and fluid homeostasis by releasing oxytocin and vasopressin into the bloodstream. However, its structure and contribution to the central actions of oxytocin and vasopressin remain incompletely understood. Using viral tracing and whole-brain imaging, we reconstruct the three-dimensional architecture of the HNS and observe collaterals of MNCs within the brain. By dual viral tracing, we further uncover that subsets of MNCs collaterally project to multiple extrahypothalamic regions. Selective activation of magnocellular oxytocin neurons promote peripheral oxytocin release and facilitate central oxytocin-mediated social interactions, whereas inhibition of these neurons elicit opposing effects. Our work reveals the previously unrecognized complexity of the HNS and provides structural and functional evidence for MNCs in coordinating both peripheral and central oxytocin-mediated actions, which will shed light on the mechanistic understanding of oxytocin-related psychiatric diseases.
The positive clinical effects caused by skin-to-skin contact immediately after birth or after repeated skin-to-skin contact of premature infants (kangaroo care) or fullterm infants are well documented in the literature. However, information regarding the physiological mechanisms mediating these effects are surprisingly scarce and incomplete. In this article the oxytocinergic system and the cutaneous sensory pathways by which the oxytocinergic system is activated in response to skin-to-skin contact are presented in more detail. In addition, we discuss how the effects of skin-to-skin treatment can be attributed to different aspects of the effect spectrum of the oxytocinergic or calm and connection system.
The structure of the oxytocinergic system, comprising the peripheral (circulating, hormonal) and the central (neurotransmitter) components, as well as, the pathways and mechanisms by which these functions are coordinated are described. Also the various effects induced by the oxytocinergic system (the calm and connection system) are reviewed.
The sensory pathways, which include visual, auditory, olfactory and tactile stimuli, given and received by both mother and newborn and which activate the oxytocinergic system in response to skin-to-skin contact, are reviewed. A special emphasis is placed on the role of cutaneous sensory nerves and their activation by touch, light pressure and in particular warmth. The important role of the rise and the pulsatility of maternal temperature in mediating the positive effects of skin-to-skin contact in the newborn is highlighted. The concept of maternal giving of warmth and its possible link to the experience of trust and safety in the newborn is discussed from an evolutionary perspective.
The effects induced by skin-to-skin contact can be attributed to the different functions of the oxytocinergic system. Ameliorated social interaction (e.g., more tactile and auditory interaction, more sensitive and synchronous interaction between mother and baby, the baby’s crawling behavior) are expressions of oxytocin’s ability to stimulate social interaction. The decreased levels of fear and stress are expressions of oxytocin’s ability to reduce the activity of the amygdala and of the stress system, e.g. the activity in the HPA-axis and the sympathetic nervous system. Increased HRV, increased activity in endocrine system of the gastrointestinal tract as well as stimulation of growth and maturation are examples of oxytocin’s ability to stimulate the activity of the parasympathetic nervous system and other peripheral and central mechanisms related to restoration and growth.
The propensity of different types of treatment with skin-to-skin contact to induce long-term effects is also highlighted. We propose that the sustained effects caused by skin-to-skin contact are induced by an enduring shift in the balance between the oxytocinergic system (the calm and connection system) and the stress system (fight flight reaction) in favor of the oxytocinergic system. This shift leads to a sustained decrease in the HPA-axis and the sympathetic nervous system probably involving alpha 2-adrenoceptors.
It is of clinical importance to be aware of the mechanisms by which skin-to-skin contact induces short and longterm positive effects in parents and newborns. If ward routines are adapted to ascertain a maximal stimulation of these mechanisms, the function of the oxytocinergic system will be optimized, which will be linked to a better clinical outcome for parents and newborns.
Oksitosin psikoloji araştırmalarını oldukça etkileyen, bağlanma, sosyal işlevler, hayatta kalma, duygusal yüz ifadelerini tanımlama, sosyal ilişkiler, aşk, üreme, ebeveynlik ve çocuk bakımı gibi birçok temel konuda etkin rol oynadığı düşünülen bir hormondur. Sosyal etkileşim olmadığında insanların üreme davranışında, gelişiminde ve hatta hayatta kalmasında sorunlar yaşaması kaçınılmaz olduğu düşünülmektedir. Sosyal etkileşimi kolaylaştırdığı öne sürülen oksitosin türü peptidlerin oluşumundan sorumlu genlerin 700 milyon yıl önce evrildiği ileri sürülmektedir. Beyindeki ve kandaki oksitosin miktarı türlere göre değişiklik göstermekte ve oksitosin seviyesindeki bireysel farklılıklar sosyal davranışlarını da içeren şekilde kişilik özellikleriyle ilişkilendirilmektedir. Oksitosin miktarı kadınlarda emzirme döneminde zirve yapmaktadır ve sütün gelmesini kolaylaştırıp anne-bebek arasındaki sosyal ve hormonal ilişkinin kurulmasına katkı sağlamaktadır. Sosyal ilişkilerdeki bağı güçlendirip olumlu ipuçlarının yakalanmasını arttırmaktadır. Böylece stresle tetiklenen kortizon salınımını baskılayarak kaygıyı azaltıp, güven ortamı sağlayarak olumlu ilişkilerin kurulmasında aracılık etmektedir. Güvenli bir ortam oluşturulduğunda sosyal davranışlarda korkusuz ya da daha rahat ilişkide bulunmayı sağlayarak sevgi dolu ilişkiler oksitosinin davranışsal etkileriyle desteklenerek sağlanabilmektedir. Ayrıca oksitosin kullanımının otizm, madde bağımlılığı, şizofreni, travma sonrası stres bozukluğu, sosyal fobi ve saldırganlık, gibi birçok psikiyarik hastalıkların tedavisinde uygulandığı ve katkı sağladığı ileri sürülmektedir. Kişilik oluşumu gibi sosyal davranışlarımız temelinde bulunan kişiliğin de oksitosin miktarıyla ilişkili olduğu düşünülmektedir. Sosyal yaşamı önemli derecede etkileyen oksitosinin fizyolojik, davranışsal ve bilişsel yönlerini araştıracak disiplinlerarası çalışmalara ihtiyaç duyulmaktadır. Bu makalede oksitosinin nörobiyolojik temelleri ve sosyal yaşamımızdaki önemi üstünde durulmuş olup davranışsal doğurguları allostatik, korku/stres, sosyo-evrimsel ve sosyal belirginlik kuramları bağlamında tartışılmıştır.
The scientific literature often uses terms such as “limbic structures” or “limbic system” to describe regions of the nervous system that participate in emotional pro- cesses. Nonetheless, these concepts have been thoroughly revised over the last 150 years and there is no clear consensual definition for which regions are actually “lim- bic” or otherwise. This chapter will summarize the evolution of the concept of a limbic system and discuss the main neural structures that are credited as taking part in the elaboration and perception of emotional states.
Keywords: Limbic system, emotions, large scale brain networks.
Oxytocin, a neuropeptide synthesized by the hypothalamus, plays a central role in human social behavior, social cognition, anxiety, mood, stress modulation, and fear learning and extinction. The relationships between oxytocin and psychiatric disorders including depression, anxiety, schizophrenia, and autism spectrum disorder have been extensively studied. In this chapter, we focus on the current knowledge about oxytocin and anxiety disorder. We discuss the anxiolytic effects of oxytocin in preclinical and clinical findings, possible related neurobehavioral mechanisms (social cognition, fear learning, and extinction), related neurotransmitter and neuroendocrine systems (hypothalamus-pituitary-adrenal axis, serotoninergic, and GABAergic systems), and studies regarding plasma levels of oxytocin, genetic and epigenetic findings, and effects of intranasal oxytocin in DSM-5 anxiety disorder (primarily social anxiety disorder and separation anxiety disorder) patients.
The greatest and last frontier of the world is within ourselves, or between two distinct worlds, our nervous system, brain-mind relationship and mind-body, our origin and end have always been a mystery to humanity. We are curious beings and always alert, interacting strongly with the environment in which we live, and clearly human nutrition directly influencing all those processes that involve growth, integration, maintenance, development and death.
Current studies indicate that oxytocin neuropeptide influence processes of perception, attention and learning that underlie social behaviour. There is a growing interest in the use of oxytocin as a treatment for memory-related psychological disorders and social cognitive disorders. Recent studies also have shown that the effect of oxytocin on social and cognitive functions greatly varies, even leading to reverse results. The factors that lead to the impacts of oxytocin and its underlying processes on such variabilities stay uncertain. In this mini-review, we intend to examine various theories regarding the effect of oxytocin on memory, along with the mechanisms which are proposed from human and animal experiments.
The aim of the present investigation was to explore whether the personality characteristics of women who have recently given birth differ from those of a control group of similar aged women and if so, whether such deviations are related to the pregnancy- and lactation-associated hormones oxytocin and prolactin which in animal experiments have been shown to play a role in maternal behavior. Thereforethe Karolinska Scales of Personality (KSP) were used in 50 women 4 days postpartum and in addition 18 blood samples were drawn in connection with breastfeeding. Oxytocin and prolactin levels were measured by radioimmunoassay. The women investigated scored lower in Muscular Tension (p < 0.05), in Monotony Avoidance (p < 0.001) and Psychasthenia (p < 0.01) and higher in Social Desirability (p < 0.001) than a reference material. Plasma levels of oxytocin and prolactin rose as expected in response to breastfeeding. When the average prolactin and oxytocin levels obtained at the 18 different timepoints of each woman were correlated with the scores obtained in the various KSP items, some significant relationships were found. Significant positive correlations were found between prolactin and the KSP dimensions Social Desirability and Inhibited Aggression and negative correlations with Psychasthenia. Significant inverse relationships between oxytocin and several Anxiety and Aggression variables, Guilt in particular, were also found. Correlations with oxytocin and prolactin levels were as a rule particularly clear in samples collected during breastfeeding. The data obtained are discussed from a biological point of view in relation to the specific 'maternal behavior' described in other mammals. It is suggested that subtle psychological and behavioral changes occur in women during motherhood and that these changes may in part be related to prolactin and oxytocin.
The aim of the present study was to investigate whether amperozide, an antipsychotic drug which possesses anti-aggressive and anxiolytic-like properties, stimulates the secretion of oxytocin and if so, by which receptor mechanism. For this purpose, female or male Sprague Dawley rats were given amperozide (0.5, 2.5 and 5.0 mg/kg IP), ritanserin (5.0 mg/kg), raclopride (2.0 mg/kg) and prazosin (1.0 mg/kg) and were subsequently decapitated for collection of blood (30 and 120 min) after injection. Oxytocin levels were measured with radioimmunoassay. Amperozide 2.5 and 5 mg/kg increased plasma levels of oxytocin significantly (P<0.05 and <0.001). The effect appeared maximal about 30 min after injection of the drug and oxytocin levels were almost back to basal within 120 min. Similar effects were obtained in female and male rats as well as in animals that were freely fed or food deprived for 24 h. CSF levels of oxytocin were also increased. Ritanserin, a 5-HT2-receptor antagonist but not the D2 receptor antagonist raclopride or the 1-adrenoceptor antagonist prazosin stimulated oxytocin release. In addition, clozapine, a neuroleptic with potent HT2-antagonistic properties, was a potent releaser of oxytocin, whereas haloperidol was without effect. A possible role for oxytocin in the behavioural effects of amperozide and clozapine remains to be explored.
Several classes of drugs that modify serotonin (5-HT) neurotransmission are either currently used, or are being evaluated for their potential use in the treatment of anxiety, schizophrenia, and depression. 5-HT1A agonists are considered potential anxiolytics, while some atypical antipsychotics are potent 5-HT2 antagonists (and also have modest dopamine D2 affinity). Furthermore, there is a diverse group of serotonergic drugs that may be effective antidepressants. Secretion of ACTH, corticosterone/cortisol, prolactin, renin, oxytocin and vasopressin are stimulated by activation of different 5-HT receptor subtypes, while other neurotransmitter receptors also influence the secretion of these hormones. We compared the receptor binding profiles of 5-HT anxiolytics, antipsychotics and antidepressants with their endocrine effects. These comparisons could aid in understanding both the therapeutic and side effects of these drugs.
The neurohypophyseal hormone oxytocin has been implicated in many aspects of reproduction including sexual behavior. This review considers the hypotheses that oxytocin and/or the neural events surrounding the release of oxytocin may have behavioral effects during sexual arousal, orgasm, sexual satiety and other aspects of sociosexual interactions.
Oxytocin, the peptide well-known for its hormonal role in parturition and lactation, is present in several extrahypothalamic brain areas besides the neurohypophyseal system. The peptide is found in neurons which send their projections to brain areas containing specific oxytocin-binding sites. Oxytocin is also released from its synapses in a calcium-dependent fashion and may be the precursor of potent behaviorally active neuropeptides. These findings suggest that this ancient neuropeptide acts as a neurotransmitter in the central nervous system. We have attempted to review the most recent behavioral, morphological, electrophysiological and neurochemical studies providing evidence that oxytocin plays an important role in the expression of central functions, such as maternal behavior, sexual behavior (penile erection, lordosis and copulatory behavior), yawning, memory and learning, tolerance and dependence mechanisms, feeding, grooming, cardiovascular regulation and thermoregulation.
A new, photocell-equipped, activity meter is described. The motor activity is observed in a large square, "open field", arena (approximately 0.5 m2) suited for activity observations of rats or other similarly sized animals. Horizontal and vertical activity is recorded at two levels (8 x 8 photocells at each level). Information from each photocell, individually fed into a microcomputer, was used to measure total motor activity, activity in the periphery of the arena, forward locomotion, rearing (total and peripheral), and speed of movement. The equipment has been evaluated by studying the effects of six psychoactive compounds, d-amphetamine, apomorphine, phencyclidine, raclopride, haloperidol, and 8-hydroxy-2-(di-n-propylamino) tetralin. In addition, a graph on the distribution of time intervals between successive photocell beam interruptions, and the within- and between-session habituation in normal animals is provided.
The substituted benzamide drug raclopride, [((-)-(S)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl) methyl)-6-methoxy-salicylamide tartrate; FLA 870(-); A40664] was shown to be a potent and selective antagonist of dopamine D-2 receptors by its high affinity for striatal 3H-spiperone binding sites and low potency to block dopamine stimulated adenylate cyclase in vitro. In vitro studies showed that 3H-raclopride binds with a high affinity (KD = 1.2 nM) and a low proportion of non-specific binding to rat striatal homogenates. The binding of 3H-raclopride is saturable (Bmax = 23.5 pmoles/g wet wt) and reversible (dissociation half-time = 30 min) with a regional distribution of the specifically bound drug showing the following rank-order: striatum greater than nucleus accumbens greater than olfactory tubercle greater than septum greater than hypothalamus greater than hippocampus greater than frontal cortex. After in vivo administration, 3H-raclopride accumulates preferentially in dopamine rich brain areas with approximately 10 times higher levels in the striatum than in the cerebellum, when examined 30 min after injection. The in vivo binding of 3H-raclopride was saturable, reversible and showed a low component of non-specific binding. More than 90% of the drug reached the brain in a non-metabolized form as judged by thin-layer chromatography. Pharmacological analysis of 3H-raclopride binding showed that it could be displaced by dopamine agonists and antagonists but not by serotoninergic or noradrenergic drugs. Taken together, the results suggest that 3H-raclopride labels dopamine D-2 receptors with high specificity in the rat brain both in vitro and in vivo, and thus, that it should be a useful tool in studies of central dopamine D-2 receptors.
This paper examines the concept of emotionality, particularly in relation to measures taken in ‘novel environment’ tests (e.g. the open field). Evidence of several different types is reviewed to assess the validity of the measures in relation to common assumptions underlying their use. In response to increased light and noise, open field defecation increases and ambulation decreases, and thus on this basis they may be termed emotional responses. In many cases defecation and ambulation in the open field showed a fairly low but significant inverse correlation. Nevertheless, a number of limitations to this relationship were found, depending on the species, strain, sex, sample size, and early experience; other, presumed, measures of emotionality in the open field showed little consistent relationship to defecation, but the evidence here was sparse. Studies measuring heart-rate responses provided insufficient evidence to relate open field defecation to this other response presumed to be under sympathetic nervous control. Ambulation showed little descriptive validity as a measure of exploration; owing to the occurrence of both immobility and escape behaviour as alternative forms of emotional behaviour, ambulation also provided an inadequate indication of emotional responses. Thus, conceptual frameworks which suggested that emotionality energized ambulation in a consistent manner were criticized. Open field defecation showed little relationship to supposed measures of emotionality taken in other types of tests (e.g. emergence tests, active avoidance learning); these findings clearly failed to support the use of emotionality as a consistent constitutional trait, with unitary drive properties. Two alternative methods were suggested, for testing: (a) responses to novel environments, and (b) emotional behaviour, without making assumptions that the measures represent unitary major motivational constructs.
The clearance of neurohypophysial peptides from cerebrospinal fluid (CSF) in conscious unrestrained guinea pigs. 125I-labelled peptides were detectable in the cisterna magna within 2 min of their intracerebroventricular injection, reaching peak concentrations 10-15 min post-injection and declining exponentially over the next hour. 125I-oxytocin (125I-OT) and 125I-vasopressin (125(I-AVP) were cleared at similar rates, whereas 125I-labelled neurophysin (125I-NP) disappeared significantly more slowly; mean half-times of clearance (t1/2) from cisternal CSF were 28, 24 and 46 min, respectively. 125I-NP was cleared at the same rate as 3H-inulin (t1/2 40 min), as was an antibody to OT (anti-OT, t1/2 37 min). Intracerebroventricular infusions of iodinated peptides produced constant levels in CSF within 3 h. 125I-AVP reached lower plateau levels and disappeared twice as fast as 125I-NP, although the apparent equilibrium distribution space was the same for both peptides. Although NP was cleared half as fast as OT or AVP, this difference was not sufficient to account for the large molar excess of NP over the nonapeptides in guinea pig CSF. There is an effective blood/CSF barrier to neurohypophysial peptides in the guinea pig; intravenous infusions of OT or porcine NP did not raise the CSF levels of these peptides (measured by specific radioimmunoassays) except when very high concentrations were maintained in peripheral plasma. However, single intravenous injections of anti-OT produced low but significant titres in CSF, persisting for several days.
Pharmacology of medazolam
- M Gerold
- M Pieri
- L Cook
- W Haefely
Gerold, M.; Pieri, M.; Cook, L.; Haefely, W. Pharmacology of medazolam. Arz-neimittelforschung 31:2180-2200; 1981.
Maternal behavior The physiology of reproduction
- M Numan
Numan, M. Maternal behavior. In: Knobil, E., et al., eds. The physiology of reproduction. New York: Raven Press; 1988:1569-1644.
Vasopressin, oxytocin and their related neuro-physins Handbook of chem-ical neuroanatomy
- M V Sofroniew
Sofroniew, M. V. Vasopressin, oxytocin and their related neuro-physins. In: Bj6rklund, A.; H6kfelt, T., eds. Handbook of chem-ical neuroanatomy. Amsterdam: Elsevier Science Publishers; 1985:93-165.
Pharmacology of medazolam
- Pieri
Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats
- Uvnäs-Moberg
Vasopressin, oxytocin and their related neurophysins
- Sofroniew