Central Oxytocin Research Articles

Changes in Serum Oxytocin Levels under Physiological and Supraphysiological Gonadal Steroid Hormone Conditions in Women of Reproductive Age: A Preliminary Study.

Oxytocin (OT) affects many behavioral, psychological, and physiological functions, including appetite and body weight regulation. Central and peripheral OT levels are markedly affected by gonadal steroids, especially estrogen, and the anorectic effects of estrogen are partially mediated by OT in rodents. In this study, the relationship between the estrogen milieu and serum OT levels was evaluated in women of reproductive age under physiological (n = 9) and supraphysiological estrogenic conditions (n = 7). Consequently, it was found that serum OT levels were increased in physiological (the ovulatory phase) and supraphysiological (on the day of the human chorionic gonadotropin trigger in an ovarian stimulation cycle) estrogenic conditions, and that serum OT levels were positively correlated with serum estradiol levels. On the other hand, serum OT levels were negatively correlated with serum progesterone levels, and there was no correlation between serum and follicular OT levels. These results suggest that OT levels may be positively and negatively regulated by estrogen and progesterone, respectively, in humans. However, the physiological roles of these actions of gonadal steroids on OT remain unclear.

Adolescence Predatory Risk Alters Social Behaviors and Cognitive Ability and Central Oxytocin and Vasopressin Expression in Adult Brandt’s Voles

Introduction: Stress during adolescence causes long-term behavioral changes in adulthood. We previously found that adolescent exposure to predatory risk augments adolescent social contact and adult parental behavior in Brandt’s voles (Lasiopodomys brandtii). Methods: Here, we determined whether this experience alters sexual behavior, pair-bond formation, and recognition ability as well as basal HPA axis activity, central oxytocin (OT), and arginine-vasopressin (AVP) expression in adulthood. Results: In the social interaction test, repeated cat odor (CO) exposure enhanced the frequency of lordosis by female voles toward an unfamiliar opposite-sex conspecific. CO voles preferred to engage with their partners after 48-h cohabitation whereas the control groups did not, which may reflect stable pair bonds in the CO treatment group. Furthermore, adolescent exposure to CO inhibited novel object recognition and place recognition ability, while it influenced social recognition only among adult males. No effect of adolescent CO exposure was observed for basal HPA axis activity, showing a habituation effect. Finally, we found that CO exposure increased OT and decreased AVP expression in the hypothalamus, including the paraventricular nucleus and anterior hypothalamus. The levels of OT in the medial amygdala were lower, and AVP in the lateral septum was higher in CO voles compared with the control. Conclusion: These findings demonstrate that adolescent exposure to predator risk promotes adult reproductive behavior of Brandt’s voles. Deficits in recognition ability may necessitate alterations in reproductive strategies to enhance inclusive fitness. OT and AVP systems may play a modulatory role in the alteration of social behaviors elicited by adolescent predatory risk.

An Overview of Oxytocin: Chemical Structure, Receptors, Physiological Functions, Measurement Techniques of oxytocin, and Metabolism

Background: Oxytocin is a peptide hormone comprising 9 amino acids. It is produced in the hypothalamus and stored and secreted by the posterior lobe of the pituitary gland and synthesized in other organs such as the uterus, ovaries, placenta, heart, blood vessels, skin, kidneys, and testis. Receptors of oxytocin are present on myoepithelial cells, heart, blood vessels, macrophages, thymus, pancreas, kidneys, and adipocytes. Objectives: The current review aimed to give highlight the oxytocin structure, receptors, physiological functions, measurement techniques, and metabolism. Oxytocin is a small peptide that consists of nine amino acids in a six–amino acid ring formed by cysteine bonds and a three–amino acid tail with a terminal amine. It is synthesized in brain regions that are critical to behavioral and physiologic homeostasis. Oxytocin is involved in uterine contraction during labor and ejection of milk during breastfeeding and plays a role in social behavior, emotions love and affection, the period after childbirth, and metabolic functions. The action of oxytocin in facilitating human bonding and social relation is well known. The effects of Oxytocin on metabolism and food intake suggesting its potential effects in treating obesity. The half-life time of oxytocin in the brain is triple as long as its half-life time in the periphery. The sensitivity and density of oxytocin receptors increase during labor. After birth, the neonatal baby sucks on his mother's breast, causing the release of milk by stimulating hypothalamic neurons to produce oxytocin. Oxytocin neurons have been heavily implicated in mediating sexual behavior in both humans and animals. The social memory was enhanced by central oxytocin administration in male rats. The action of oxytocin affects social memory in multiple brain regions, including the ventral hippocampus, amygdala, olfactory bulb, and lateral septum. Oxytocin neurons may mediate MC4R-driven sexual behavior in male mice. MC4R signaling in oxytocin neurons permits ejaculation. A decreased latency to ejaculate in rabbits and rats after administration of oxytocin. The effect of oxytocin receptor ligands on the ejaculatory response may be due to the modulation of dopamine serotonin neurotransmission. Oxytocin lowers the threshold for the initiation of maternal behavior but is not involved in its maintenance. The oxytocin and the melanin-concentrating hormone (MCH) systems may interact to modulate maternal behavior. Oxytocin regulates maternal- or mating-regulated mood. Initial measurements of oxytocin by using radioimmunoassay and bioassays suggested that oxytocin concentration in blood is very low, 5 pg/ml, with small increases as pulses,15 pg/ml, during lactation and uterine contractions. Variations in oxytocin concentration, especially in rapid response to specific experiences, such as anticipation of breastfeeding, sexual stimulation, exercise, affiliative social contact, and psychologic stress. Oxytocin is rapidly removed from the plasma by the liver and kidney. Oxytocinase activity increases throughout pregnancy and peaks in the plasma, placenta, and uterus near term. It is also expressed in mammary glands, the heart, the kidney, and the small intestine. Lower levels of activity can be found in the brain, spleen, liver, skeletal muscle, testes, and colon. The plasma half-life of oxytocin ranges from 1 to 6 minutes. The half-life is decreased in late pregnancy and during lactation. Conclusion: It can be concluded that oxytocin is a peptide hormone that is synthesized in brain regions and other organs and posse's receptors in many organs. It plays a role in social behavior, emotions love, and affection, the period after childbirth, and metabolic functions. Its potential effects in treating obesity. The half-life time of oxytocin in the brain is triple as long as its half-life time in the periphery. Oxytocin neurons may mediate MC4R-driven sexual behavior. Variations in oxytocin concentration, especially in rapid response to specific experiences. Oxytocin is rapidly removed from the plasma by the liver and kidney. The plasma half-life of oxytocin ranges from 1-6 minutes. The half-life is decreased in late pregnancy and during lactation.

Oxytocin in Huntington's disease and the spectrum of amyotrophic lateral sclerosis-frontotemporal dementia.

Neurodegenerative disorders (NDDs) such as Huntington’s disease (HD) and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by progressive loss of selectively vulnerable populations of neurons. Although often associated with motor impairments, these NDDs share several commonalities in early symptoms and signs that extend beyond motor dysfunction. These include impairments in social cognition and psychiatric symptoms. Oxytocin (OXT) is a neuropeptide known to play a pivotal role in the regulation of social cognition as well as in emotional behaviors such as anxiety and depression. Here, we present an overview of key results implicating OXT in the pathology of HD, ALS and FTD and seek to identify commonalities across these NDDs. OXT is produced in the hypothalamus, a region in the brain that during the past decade has been shown to be affected in HD, ALS, and FTD. Several studies using human post-mortem neuropathological analyses, measurements of cerebrospinal fluid, experimental treatments with OXT as well as genetic animal models have collectively implicated an important role of central OXT in the development of altered social cognition and psychiatric features across these diseases. Understanding central OXT signaling may unveil the underlying mechanisms of early signs of the social cognitive impairment and the psychiatric features in NDDs. It is therefore possible that OXT might have potential therapeutic value for early disease intervention and better symptomatic treatment in NDDs.

Expression of oxytocin in hypothalamus and reduction of nociceptive stress following administration of Kamikihi-to in female rats

Hypothalamo-neurohypophysial oxytocin (OXT) plays an essential role in reproduction and in several socio-physiological functions, including stress reduction, anxiety relief, feeding suppression, social recognition, and trust building. Recent studies suggest that the central OXT system is also involved in antinociceptive and anti-inflammatory functions. Kamikihi-to (KKT), a Japanese traditional herbal (Kampo) medicine composed of 14 herbal ingredients, is clinically prescribed for patients with psychological symptoms, including anxiety, depression, and insomnia, and it has been associated with OXT expression. We investigated the antinociceptive response and OXT expression according to sex and the effects of KKT pre administration in a rat model. We found that nociceptive responses measured via the hot plate and formalin tests were attenuated following the administration of KKT-enriched feed for 4 weeks. The observation of mRFP1 fluorescence in OXT-mRFP1 transgenic rats revealed that KKT-administered rats showed increased expression of OXT in the magnocellular and parvocellular paraventricular nucleus of the hypothalamus. Food intake in the KKT-pre-administered group significantly decreased after cholecystokinin (CCK)-8 administration. Our results suggest that KKT is involved in the attenuation of nociceptive stress in female rats by enhancing the expression of OXT in the hypothalamus.

Recording and manipulation of the maternal oxytocin neural activities in mice

Pulsatile release of the hormone oxytocin (OT) mediates uterine contraction during parturition and milk ejection during lactation.1-3 These pulses are generated by the unique activity patterns of the central neuroendocrine OT neurons located in the paraventricular and supraoptic hypothalamus. Classical studies have characterized putative OT neurons by invivo extracellular recording techniques in rats and rabbits.1,4-10 Due to technical limitations, however, the identity of OT neurons in these previous studies was speculative based on their electrophysiological characteristics and axonal projection to the posterior pituitary, not on OT gene expression. To pinpoint OT neural activities among other hypothalamic neurons that project to the pituitary11,12 and make better use of cell-type-specific neuroscience toolkits,13 a mouse model needs to be developed for the studies of parturition and lactation. We herein introduce viral genetic approaches in mice to characterize the maternal activities of OT neurons by fiber photometry. A sharp photometric peak of OT neurons appeared at approximately 520s following simultaneous suckling stimuli from three pups. The amplitude of the peaks increased as the mother mice experienced lactation, irrespective of the age of the pups, suggesting the intrinsic plasticity of maternal OT neurons. Based on a mono-synaptic input map to OT neurons, we pharmacogenetically activated the inhibitory neurons in the bed nucleus of the stria terminalis and found the suppression of the activities of OT neurons. Collectively, our study illuminates temporal dynamics in the maternal neural activities of OT neurons and identifies one of its modulatory inputs.

Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats

Brain oxytocin plays a role in gastrointestinal functions. Among them, oxytocin acts centrally to modulate gastrointestinal motility and visceral sensation. Intestinal barrier function, one of important gut functions, is also regulated by the central nervous system. Little is, however, known about a role of central oxytocin in the regulation of intestinal barrier function. The present study was performed to clarify whether brain oxytocin is also involved in regulation of intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of oxytocin dose-dependently abolished increased colonic permeability in response to lipopolysaccharide while intraperitoneal injection of oxytocin at the same dose failed to block it. Either atropine or surgical vagotomy blocked the central oxytocin-induced improvement of colonic hyperpermeability. Cannabinoid 1 receptor antagonist but not adenosine or opioid receptor antagonist prevented the central oxytocin-induced blockade of colonic hyperpermeability. In addition, intracisternal injection of oxytocin receptor antagonist blocked the ghrelin- or orexin-induced improvement of intestinal barrier function. These results suggest that oxytocin acts centrally in the brain to reduce colonic hyperpermeability. The vagal cholinergic pathway or cannabinoid 1 receptor signaling plays a vital role in the process. The oxytocin-induced improvement of colonic hyperpermeability mediates the central ghrelin- or orexin-induced improvement of intestinal barrier function. We would therefore suggest that activation of central oxytocin signaling may be useful for leaky gut-related diseases such as irritable bowel syndrome and autism.

Thyroid Supplementation Reverses the Abnormal Social and Oxytocin Phenotype Produced by Developmental Exposure to PBDEs in a Sex‐Dependent Manner

Polybrominated diphenyl ethers (PBDEs) are endocrine‐disrupting chemicals (EDCs) that are widely used flame retardants added to common household products. In humans, PBDEs are associated with neurodevelopmental deficits including ones associated with social competence and learning. We have previously shown that PBDE‐exposed F1 female progeny display autism‐relevant characteristics such as deficient social novelty preference and social recognition memory (SRM), exaggerated repetitive behavior and deficient social odor discrimination (Kozlova et al 2021). In this study, we show that developmental exposure (via dam GD0‐PND21) to the PBDE mixture, DE‐71 (L‐DE‐71; 0.1 mg/kg/d), reduces oxytocin immunofluorescence density in the paraventricular nucleus of the hypothalamus (PVN) that is critical for social recognition memory in male and female F1 offspring relative to VEH/CON (0 mg/kg/d). One of the well characterized actions of PBDEs is disruption of the hypothalamo‐pituitary‐thyroid axis (HPT). Thyroid hormones (TH) are critical for nervous system development and regulate the transcription of oxytocin. We show for the first time, that L‐DE‐71 alters central thyroid hormone species (T2, rT3, T3, and T4) relative to VEH/CON in F1 offspring but with a different temporal pattern in males (PND30) and females (PND15) as measured using liquid chromatography‐tandem mass spectrometry. This coincides with reduced plasma T4 in PND15 male but not female offspring. Supplementation of pregnant dams with levothyroxine, a synthetic analogue of thyroxine (T4), during gestation and lactation (GD12‐PND21), increased plasma oxytocin in exposed dams. More importantly, supplementation normalized PBDE‐induced deficiency in social recognition memory test, and PVN oxytocin levels in exposed female but not male offspring. These changes are specific to social behavior as were no changes in passive avoidance memory. Interestingly, L‐DE‐71 female but not male F1 also receiving supplementation showed a significant increase in plasma T4. Maternal behavior (retrieval of PND4 pups) was significantly reduced by supplementation with 6‐propyl‐2‐thiouracil, a drug that blocks the production of thyroid hormone by thyroid gland, but not by DE‐71 nor DE‐71 plus levothyroxine supplementation. These results provide novel insight into neuroendocrine disruption of the central oxytocin system by maternal transfer of environmental pollutants and its possible contribution to neurodevelopmental disorders such as autism.

Alpha-melanocyte-stimulating hormone (αMSH) modulates the rewarding properties of social interactions in an oxytocin receptor-dependent manner in Syrian hamsters (Mesocricetus Auratus)

A reduction in the rewarding properties of social interactions is frequently a key contributor to neuropsychiatric disorders. Although much remains to be learned about the neural mechanisms governing social reward, numerous studies have found that oxytocin can enhance the salience of rewarding social interactions. As a result, oxytocin has been suggested as a pharmacotherapy for disorders characterized by a dampening of social motivation. However, exogenous oxytocin does not cross the blood-brain barrier effectively, which has led to the investigation of alternative approaches to induce central oxytocin release, such as pharmaceuticals targeting melanocortins. Although oxytocin treatment is widely viewed to increase social reward, there is also recent evidence that high concentrations of oxytocin can decrease social reward. In the present study we tested the hypothesis that alpha-melanocyte-stimulating hormone (αMSH) influences the rewarding properties of social interactions by acting on oxytocin receptors. Male and female Syrian hamsters were given intracerebroventricular infusions of saline, αMSH, or a cocktail containing αMSH and an oxytocin receptor antagonist during social conditioning with a same-sex hamster and then tested for a conditioned place preference. αMSH decreased preference for the socially-paired chamber compared to saline treatment, and administration of the oxytocin antagonist concurrent with αMSH administration returned subjects’ preference to control levels. Importantly, αMSH treatments did not affect any measures of body composition or the specific social behaviors displayed during conditioning. These data suggest that melanocortin-targeting drugs should be administered carefully to avoid the possibility of decreasing the rewarding properties of social interactions.

Paternal Cocaine in Mice Alters Social Behavior and Brain Oxytocin Receptor Density in First Generation Offspring

It is well established that the damaging effects of drugs of abuse, such as cocaine, can extend beyond the user to their offspring. While most preclinical models of the generational effects of cocaine abuse have focused on maternal effects, we, and others, report distinct effects on offspring sired by fathers treated with cocaine prior to breeding. However, little is known about the effects of paternal cocaine use on first generation (F1) offspring’s social behaviors. Here, we expand upon our model of oral self-administered paternal cocaine use to address the idea that paternal cocaine alters first generation offspring social behaviors through modulation of the oxytocin system. F1 cocaine-sired males displayed unaltered social recognition vs. non-cocaine sired controls but showed increased investigation times that were not related to altered olfaction. Paternal cocaine did not alter F1 male-aggression behavior or depression-like behaviors, but cocaine-sired males did display decreased anxiety-like behaviors. Female F1 behavior was similarly examined, but there were no effects of paternal cocaine. Cocaine-sired male mice also exhibited localized oxytocin receptor expression differences vs. controls in several brain regions regulating social behavior. These results provide evidence for effects of paternal cocaine exposure on social behaviors in male offspring with associated alterations in central oxytocin transmission.

Oxytocin effects on the behavior in historical and experimental domesticated animals

Domestication is one of the important evolutionary and genetic problems of biology. It addresses fundamental evolution aspects as well as allows us to study mechanisms of aggression, pro-social behavior and anthropogenesis. One of the potential key mechanisms of domestication may be associated with the central oxytocin (OT) system. OT has been repeatedly shown to exhibit pro-social and anxiolytic eff ects rodents, dogs, humans and other species [1]. In our study, we used intranasal OT administration on Siberian tame foxes and non-selected one. It is well-known experimental domestication model of. Th e OT eff ect on behavior had been investigated in intermale interactions (triple cage aft er adaptation) and human contact (new enclosure). OT administration increased patterns of playful (crouches on paws), affi liative (friendly) behavior, motor (fast move) and mixed activity in male-to-male interactions in tame foxes, whereas in case of unselected foxes, OT administration increased behavior patterns associated with anxiety (latent time for home cage exit, freezing, total time in home cage). In fox-human interactions, OT administration had the greatest eff ect on increasing the time tamed fox stayed at less than a meter away from a human. It is this parameter that is the defi ning one in similar tests on dogs. Th e results allow to suggest that OT has a context-dependent eff ect rather than explicitly pro-social eff ect in the tests, therefore amplifying the perception of social conditions according to the social salience hypothesis of OT. OT eff ect is associated with emotional positive and negative animal behaviors toward human that could be related to the genotype. Such OT eff ect might separate animals into more or less tolerant to humans under the same early domestication conditions.

Comment, au fil du temps, l’ocytocine est devenue l’hormone de l’attachement

Oxytocin is a pleiotropic molecule which, in addition to its facilitating action during parturition and milk ejection, is involved in social and prosocial behaviors such as attachment. This article presents, after a brief historical review, the action of oxytocin during the milk ejection reflex. Oxytocin is indeed essential for this vital function in mammals. It is both a neurohormone released into the bloodstream by the axon terminals of the posterior pituitary and a neuromodulator released in the hypothalamus by the soma and dendrites of oxytocinergic magnocellular neurons. In addition, oxytocin is also released by the axon terminals of parvocellular neurons and axon collaterals of magnocellular neurons in the brain. Both maternal attachment in rats and ewes and attachment between sexual partners in the prairie vole, one of the few monogamous rodent species, are mediated by central oxytocin. However, neither administering oxytocin into the brain nor increasing expression of the oxytocin receptor in the nucleus accumbens using a gene transfer technique converts polygamous voles to monogamous ones. Unfortunately, translation of animal data to human remains problematic due to still unsolved difficulties in modifying the level of oxytocin in the brain.

Oxytocin and obsessive–compulsive disorder

Attention has recently been focused on central nervous system neuropeptides as potential mediators of the symptom profile of obsessive–compulsive disorder (OCD). OCD includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with oxytocin (OT). Increased cerebrospinal fluid levels of the anxiolytic neuropeptide OT have been reported in OCD. OT is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the central nervous system as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. OT is associated with the regulation of complex sociocognitive processes such as attachment, social exploration, social recognition, anxiety, and other stress-related behaviors. Based on these data, we hypothesized that OCD is mediated by OT. The aim of this review is to define possible involvements of OT in the pathophysiology of OCD.

Endogenous Oxytocin Levels in Autism-A Meta-Analysis.

Oxytocin (OT) circuitry plays a major role in the mediation of prosocial behavior. Individuals with autism spectrum disorder (ASD) are characterized by impairments in social interaction and communication and have been suggested to display deficiencies in central OT mechanisms. The current preregistered meta-analysis evaluated potential group differences in endogenous OT levels between individuals with ASD and neurotypical (NT) controls. We included 18 studies comprising a total of 1422 participants. We found that endogenous OT levels are lower in children with ASD as compared to NT controls (n = 1123; g = −0.60; p = 0.006), but this effect seems to disappear in adolescent (n = 152; g = −0.20; p = 0.53) and adult populations (n = 147; g = 0.27; p = 0.45). Secondly, while no significant subgroup differences were found in regard to sex, the group difference in OT levels of individuals with versus without ASD seems to be only present in the studies with male participants (n = 814; g = −0.44; p = 0.08) and not female participants (n = 192; g = 0.11; p = 0.47). More research that employs more homogeneous methods is necessary to investigate potential developmental changes in endogenous OT levels, both in typical and atypical development, and to explore the possible use of OT level measurement as a diagnostic marker of ASD.

Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms.

The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which oxytocin’s anorexigenic effects occur. The research supports a framework through which oxytocin reduces food intake via amplification of within-meal physiological satiation signals rather than by altering between-meal interoceptive hunger and satiety states. We also emphasize the distributed neural sites of action for oxytocin’s effects on food intake and review evidence supporting the notion that central oxytocin is communicated throughout the brain, at least in part, through humoral-like volume transmission. Finally, we highlight mechanisms through which oxytocin interacts with various energy balance-associated neuropeptide and endocrine systems (e.g., agouti-related peptide, melanin-concentrating hormone, leptin), as well as the behavioral mechanisms through which oxytocin inhibits food intake, including effects on nutrient-specific ingestion, meal size control, food reward-motivated responses, and competing motivations.

Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances.

A continuously increasing amount of research shows that oxytocin is involved in numerous central functions. Among the functions in which oxytocin is thought to be involved are those that play a role in social and sexual behaviors, and the involvement of central oxytocin in erectile function and sexual behavior was indeed one of the first to be discovered in laboratory animals in the 1980s. The first part of this review summarizes the results of studies done in laboratory animals that support a facilitatory role of oxytocin in male and female sexual behavior and reveal mechanisms through which this ancient neuropeptide participates in concert with other neurotransmitters and neuropeptides in this complex function, which is fundamental for the species reproduction. The second part summarizes the results of studies done mainly with intranasal oxytocin in men and women with the aim to translate the results found in laboratory animals to humans. Unexpectedly, the results of these studies do not appear to confirm the facilitatory role of oxytocin found in male and female sexual behavior in animals, both in men and women. Possible explanations for the failure of oxytocin to improve sexual behavior in men and women and strategies to attempt to overcome this impasse are considered.

Brain areas affected by intranasal oxytocin show higher oxytocin receptor expression.

Neuroimaging studies suggest that intranasal oxytocin (IN‐OXT) may modulate emotional and social processes by altering neural activity patterns. The extent of brain penetration after IN‐OXT is unclear, and it is currently unknown whether IN‐OXT can directly bind central oxytocin receptors (OXTRs). We investigated oxytocin pathway gene expression in regions affected by IN‐OXT on task‐based fMRI. We found that OXTR is more highly expressed in affected than unaffected subcortical regions; this effect did not vary by task type or sex. Cortical results revealed higher OXTR expression in regions affected by IN‐OXT in emotional processing tasks and in male‐only data. No significant differences were found in expression of the closely related vasopressin receptors. Our findings suggest that the mechanism by which IN‐OXT may alter brain functionality involves direct activation of central OXTRs.

Enhancement of Oxytocin in the Medial Prefrontal Cortex Reverses Behavioral Deficits Induced by Repeated Ketamine Administration in Mice.

Ketamine is a popular recreational substance of abuse that induces persistent behavioral deficits. Although disrupted oxytocinergic systems have been considered to modulate vulnerability to developing drugs of abuse, the involvement of central oxytocin in behavioral abnormalities caused by chronic ketamine has remained largely unknown. Herein, we aimed to investigate the potential role of oxytocin in the medial prefrontal cortex (mPFC) in social avoidance and cognitive impairment resulting from repeated ketamine administration in mice. We found that ketamine injection (5 mg/kg, i.p.) for 10 days followed by a 6-day withdrawal period induced behavioral disturbances in social interaction and cognitive performance, as well as reduced oxytocin levels both at the periphery and in the mPFC. Repeated ketamine exposure also inhibited mPFC neuronal activity as measured by a decrease in c-fos-positive cells. Furthermore, direct microinjection of oxytocin into the mPFC reversed the social avoidance and cognitive impairment following chronic ketamine exposure. In addition, oxytocin administration normalized ketamine-induced inflammatory cytokines including TNF-α, IL-6, and IL-1β levels. Moreover, the activation of immune markers such as neutrophils and monocytes, by ketamine was restored in oxytocin-treated mice. Finally, the reversal effects of oxytocin on behavioral performance were blocked by pre-infusion of the oxytocin receptor antagonist atosiban into the mPFC. These results demonstrate that enhancing oxytocin signaling in the mPFC is a potential pathway to reverse social avoidance and cognitive impairment caused by ketamine, partly through inhibition of inflammatory stimulation.

Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN.

Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here, we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes; however, activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.

Possible Mechanisms of Hypnosis from an Interactional Perspective.

In this paper, utilizing the interactional research paradigm developed by Éva Bányai, we discuss the hypnotic relationship from the viewpoint of interactional synchrony. Based on our three decades of empirical studies of an interactional paradigm, we propose the analogy between hypnosis and mother–child interaction. Hypnosis is considered as a potential corrective/reparative possibility when the real childhood experiences appear to be unfavourable. Possible neuroanatomical and neurochemical mechanisms are also suggested in the right hemispheric orbitofrontal cortex and central oxytocin system.