Hypothalamic Oxytocin Research Articles

Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats.

Left ventricular (LV) electrical maladaptation to increased heart rate in failing myocardium contributes to morbidity and mortality. Recently, cardiac cholinergic neuron activation reduced loss of contractile function resulting from chronic transverse-ascending aortic constriction (TAC) in rats. We hypothesized that chronic activation of cardiac cholinergic neurons would also reduce TAC-induced derangement of cardiac electrical activity. We investigated electrophysiological rate adaptation in TAC rat hearts with and without daily chemogenetic activation of hypothalamic oxytocin neurons for downstream cardiac cholinergic neuron stimulation. Sprague–Dawley rat hearts were excised, perfused, and optically mapped under dynamic pacing after 16 wk of TAC with or without 12 wk of daily chemogenetic treatment. Action potential duration at 60% repolarization (APD60) and conduction velocity (CV) maps were analyzed for regional rate adaptation to dynamic pacing. At lower pacing rates, untreated TAC induced elevated LV epicardial APD60. Fitted APD60 steady state (APDss) was reduced in treated TAC hearts. At higher pacing rates, treatment heterogeneously reduced APD60, compared with untreated TAC hearts. Variance of conduction loss was reduced in treated hearts compared with untreated hearts during fast pacing. However, CV was markedly reduced in both treated and untreated TAC hearts throughout dynamic pacing. At 150 ms pacing cycle length, APD60 versus diastolic interval dispersion was reduced in treated hearts compared with untreated hearts. Chronic activation of cardiac cholinergic neurons improved electrophysiological adaptation to increases in pacing rate during the development of TAC-induced heart failure. This provides insight into the electrophysiological benefits of cholinergic stimulation as a treatment for patients with heart failure.NEW & NOTEWORTHY Analysis of electrophysiology from optical mapping of failing left ventricular myocardium provided insight into the possible therapeutic outcomes of cholinergic stimulation within the left ventricle. Chronic hypothalamic oxytocin neuron activation for downstream cardiac cholinergic neuron stimulation blunted onset of failing electrophysiology induced by pressure overload-induced heart failure in rats.

Oxytocin-monomeric red fluorescent protein 1 synthesis in the hypothalamus under osmotic challenge and acute hypovolemia in a transgenic rat line.

We generated a transgenic rat line that expresses oxytocin (OXT)‐monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualize the dynamics of OXT. In this transgenic rat line, hypothalamic OXT can be assessed under diverse physiological and pathophysiological conditions by semiquantitative fluorometry of mRFP1 fluorescence intensity as a surrogate marker for endogenous OXT. Using this transgenic rat line, we identified the changes in hypothalamic OXT synthesis under various physiological conditions. However, few reports have directly examined hypothalamic OXT synthesis under hyperosmolality or hypovolemia. In this study, hypothalamic OXT synthesis was investigated using the transgenic rat line after acute osmotic challenge and acute hypovolemia induced by intraperitoneal (i.p.) administration of 3% hypertonic saline (HTN) and polyethylene glycol (PEG), respectively. The mRFP1 fluorescence intensity in the paraventricular (PVN) and supraoptic nuclei (SON) was significantly increased after i.p. administration of HTN and PEG, along with robust Fos‐like immunoreactivity (co‐expression). Fos expression showed neuronal activation in the brain regions that are associated with the hypothalamus and/or are involved in maintaining water and electrolyte homeostasis in HTN‐ and PEG‐treated rats. OXT and mRFP1 gene expressions were dramatically increased after HTN and PEG administration. The plasma OXT level was extremely increased after HTN and PEG administration. Acute osmotic challenge and acute hypovolemia induced upregulation of hypothalamic OXT in the PVN and SON. These results suggest that not only endogenous arginine vasopressin (AVP) but also endogenous OXT has a key role in maintaining body fluid homeostasis to cope with hyperosmolality and hypovolemia.

Mating and parenting experiences sculpture mood-modulating effects of oxytocin-MCH signaling

The two hypothalamic neuropeptides oxytocin and melanin concentrating hormone (MCH) share several physiological actions such as the control of maternal care, sexual behavior, and emotions. In this study, we uncover the role for the oxytocin-MCH signaling pathway in mood regulation. We identify discrete effects of oxytocin-MCH signaling on depressive behavior and demonstrate that parenting and mating experiences shape these effects. We show that the selective deletion of OXT receptors from MCH neurons increases and decreases depressive behavior in sexually naïve and late postpartum female mice respectively, with no effect on sexually naïve male mice. We demonstrate that both parenting experience and mood-regulating effects of oxytocin-MCH are associated with synaptic plasticity in the reward and fear circuits revealed by the alterations of Arc expressions, which are associated with the depressive behavior. Finally, we uncover the sex-dependent effects of mating on depressive behavior; while the sexual activity reduces the basal levels of depressive behavior in male mice, it reduces in female mice evoked-depression only. We demonstrate that the oxytocin-MCH pathway mediates the effects of sexual activity on depressive behavior. Our data suggest that the oxytocin-MCH pathway can serve as a potential therapeutic target for the treatment of major depression and postpartum mood disorders.

Regular moderate exercise alleviates gastric oxidative damage in rats via the contribution of oxytocin receptors.

A moderate level of exercise has beneficial effects for the prevention of gastric ulcers. Although regular aerobic exercise was shown to elevate serum oxytocin levels and exogenously administered oxytocin exerts an anti-ulcer activity, the role of endogenous oxytocin in the gastroprotective effects of exercise has not yet been elucidated. We showed that increased anxiety and oxidative gastric damage induced by gastric ulcers were reversed in pre-exercised rats, while reduced hypothalamic oxytocin expression and decreased myenteric oxytocin receptor expression due to gastric ulcers were abolished by exercise. We also reported that the blockade of oxytocin receptors exaggerated gastric damage in exercised rats with ulcers. Our data establish that endogenous oxytocin is the key mediator in the beneficial effects of regular physical activity in alleviating gastric injury. Exercise increases serum oxytocin levels and exogenous oxytocin exerts an anti-ulcer activity; but the role of oxytocin in the protective effects of exercise against gastric ulcers has not yet been evaluated. This study was designed to investigate the impact of regular swimming exercise on oxidative gastric injury, and the role of oxytocin receptor activity in the anxiolytic and anti-inflammatory actions of exercise. Adult Wistar albino rats of both sexes performed swimming exercise (30min/day, 5days) or stayed sedentary. At the end of the 6-week exercise/sedentary protocol, rats were injected intraperitoneally with atosiban (0.1mg/kg/day) or saline for 4days. On the 5th day, under anaesthesia, acetic acid (ulcer) or saline (sham) was applied onto the gastric serosa and the treatments were continued. On the 9th day, anxiety levels were determined; gastric blood flow was measured, and blood, gastric and brain tissues were obtained. Induction of ulcers in sedentary rats increased anxiety and serum corticosterone levels; but reduced gastric blood flow and resulted in apoptosis and oxidative gastric damage with increased cytokine expressions. However, when ulcers were induced in pre-exercised rats, behavioural and biochemical alterations due to gastric damage were reversed. The inhibition of oxytocin receptors by atosiban exaggerated pro-inflammatory cytokine expressions and gastric lipid peroxidation in the stomachs of exercised rats with ulcers. When rats had regularly exercised prior to ulcer induction, reductions in the immunolabelling of hypothalamic oxytocin and myenteric oxytocin receptors were abolished, suggesting that exercise-induced alleviation of gastric injury may involve the reversal of down-regulated oxytocinergic activity.

Activation of Oxytocin Neurons Improves Cardiac Function in a Pressure-Overload Model of Heart Failure

This work shows long-term restoration of the hypothalamic oxytocin (OXT) network preserves OXT release, reduces mortality, cardiac inflammation, fibrosis, and improves autonomic tone and cardiac function in a model of heart failure. Intranasal administration of OXT in patients mimics the short-term changes seen in animals by increasing parasympathetic-and decreasing sympathetic-cardiac activity. This work provides the essential translational foundation to determine if approaches that mimic paraventricular nucleus (PVN) OXT neuron activation, such as safe, noninvasive, and well-tolerated intranasal administration of OXT, can be beneficial in patients with heart failure.

Oxytocin has sex-specific effects on social behaviour and hypothalamic oxytocin immunoreactive cells but not hippocampal neurogenesis in adult rats

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 certain central effects (oxytocin levels in the hypothalamus and neurogenesis in the ventral hippocampus) 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.

Lavender Oil Reduces Depressive Mood in Healthy Individuals and Enhances the Activity of Single Oxytocin Neurons of the Hypothalamus Isolated from Mice: A Preliminary Study.

Background The aim of the present study was to assess the effects of lavender oil inhalation on blood pressure, pulse measurements, cortisol levels, depressive mood, and anxiety in healthy male adults. The mechanism was investigated by the action on oxytocin single neurons in the hypothalamus of rodents. Methods The participants (n = 7) were aged 20–40 years. After randomisation, they received an inhaled dose of lavender oil or distilled water for 20 min. They received the other treatment after a washout period of one week. We assessed the outcomes using the Self-Rating Depression Scale, State-Trait Anxiety Inventory, and self-rated unidimensional Visual Analogue Scale for depression; anxiety; and hunger, thirst, and appetite, respectively. Blood pressure, pulse rate, and cortisol concentration in the peripheral blood were assessed before and after inhalation. In the rodent study (n = 4), oxytocin single neurons were isolated from the mouse hypothalamus. Intracellular Ca2+ concentration in the oxytocin neurons isolated from the hypothalamus was measured following direct administration of lavender oil. Results Seven participants completed the study. Lavender inhalation decreased Self-Rating Depression Scale score and systolic and diastolic blood pressure. Ex vivo administration of lavender oil increased intracellular Ca2+ concentration in the hypothalamic oxytocin neurons. Conclusions Lavender oil might be a useful therapy for stress relief, and its mechanism of action may include activation of the central oxytocin neurons.

Metabolic Effects of Oxytocin.

There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader-Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX - XX, 2020).

The Effect of Oxytocin on Reparative Histogenesis in the Periodontium and Mucous Membrane of the Airways (Experimental Study)

The aim of the study was to elucidate the role and significance of oxytocin in reparative histogenesis of tissues of various genesis using the example of periodontal tissues and extrapulmonary airways.Material and methods. Periodontitis and tracheobronchitis were simulated on sexually mature white outbred male rats. Periodontitis was simulated by traumatic injury to the periodontium, followed by the wound infection with Staphylococcus aureus. Introduction of oxytocin as an additional tool was used in the treatment of periodontitis. Experimental tracheobronchitis was simulated in rats by intratracheal infection with S. aureus (strains with and without antilactoferrin activity). Paraventricular large-cell nuclei of the hypothalamus were additionally destroyed in the simulated experimental tracheobronchitis (in order to reduce the production of endogenous oxytocin). The resulting material (the periodontium, alveolar processes, trachea and extrapulmonary bronchi) was examined using histological methods of investigation.Results. Analysis of histological sections demonstrated that when oxytocin was used in the complex therapy of experimental periodontitis, the proliferation and cyto-differentiation of fibroblasts, osteoblasts and cementoblasts was intensified, followed by their activation; this resulted in the optimization of reparative histogenesis in the structures of the periodontium and alveolar ridge. In animals with destruction of the paraventricular nuclei of the hypothalamus (against the background of an oxytocin deficiency in the body), a decrease in the reparative potential of the tracheal and bronchial mucosa was observed. Moreover, the severity of the inflammatory process in the mucous membrane of the trachea and bronchi with the introduction of staphylococci with antilactoferrin activity was significantly higher than that of animals that were administered staphylococci without antilactoferrin activity.Conclusion. The results obtained indicate the optimizing and correcting effect of the hypothalamic nonapeptide oxytocin on the reparative regeneration of the studied periodontal and the trachea and bronchi structures.

Zebrafish oxytocin neurons drive nocifensive behavior via brainstem premotor targets.

Animals have evolved specialized neural circuits to defend themselves from pain- and injury-causing stimuli. Using a combination of optical, behavioral and genetic approaches in the larval zebrafish, we describe a novel role for hypothalamic oxytocin (OXT) neurons in the processing of noxious stimuli. In vivo imaging reveals that a large and distributed fraction of zebrafish OXT neurons responds strongly to noxious inputs, including the activation of damage-sensing TRPA1 receptors. OXT population activity reflects the sensorimotor transformation of the noxious stimulus, with some neurons encoding sensory information and others correlating more strongly with large-angle swims. Notably, OXT neuron activation is sufficient to generate this defensive behavior via the recruitment of brainstem premotor targets, whereas ablation of OXT neurons or loss of the peptide attenuate behavioral responses to TRPA1 activation. These data highlight a crucial role for OXT neurons in the generation of appropriate defensive responses to noxious input.

A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System

Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram.

SUN-101 Dysregulation of Hypothalamic Gene Expression by Soybean Oil Diets in Mice

Soybean oil is a major component of the American diet and its increased consumption correlates positively with the prevalence of obesity and diabetes in the U.S. Our previous findings showed that a high fat diet (HFD) enriched in soybean oil, similar to the American diet, induces more obesity, diabetes, insulin resistance and fatty liver in male mice than an isocaloric diet consisting of coconut oil (CO), as well as a substantial dysregulation of liver gene expression (PMID:28970503, 26200659). Here, RNA-seq analysis reveals that HFDs based on conventional soybean oil (SO), which is high in linoleic acid (LA), and a genetically modified, low-LA soybean oil called Plenish, have similar, albeit non identical, effects on hypothalamic gene expression; in contrast, a CO HFD has a negligible effect compared to the low fat vivarium chow (Viv) diet. Genes related to inflammation and oxidative stress, metabolism, obesity and diabetes, as well as those linked to neurological disorders, are dysregulated by SO and Plenish. Oxt, which encodes the neuropeptide oxytocin (OXT), is the only gene with metabolic and neurological significance upregulated by both soybean oil diets, but not CO, suggesting that Oxt gene expression is altered by neither LA nor the saturated fatty acids present in CO. In contrast, immunohistochemistry (IHC) shows that the two soybean oil diets reduce oxytocin protein (OXT) levels in the supraoptic and paraventricular nuclei of the hypothalamus, while OXT peptide levels are increased in the circulating blood, suggesting that a decrease in hypothalamic OXT may be responsible for SO-induced obesity and diabetes. The phytosterol stigmasterol found in both the SO and Plenish diets did not induce either obesity or diabetes nor affect the oxytocin pathway, suggesting that a component in soybean oil other than LA or stigmasterol is responsible for its metabolic effects. Given the impact that Oxt can have on metabolic processes as well as developmental disorders of social behavior including autism, depression and schizophrenia, the American diet based largely on soybean oil may have a broader impact on human health than previously appreciated.(Funding: NIH NIDDK, NIEHS T32, CCFA, Seed Grant-UCR).

Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat

Despite the high incidence of neuropathic pain, its mechanism remains unclear. Oxytocin (OXT) is an established endogenous polypeptide produced in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. OXT, which is synthesized by OXT neurons in the SON and the magnocellular part of the PVN (mPVN), is delivered into the posterior pituitary (PP), then released into the systemic blood circulation. Meanwhile, OXT-containing neurosecretory cells in the parvocellular part of the PVN (pPVN) are directly projected to the spinal cord and are associated with sensory modulation. In this study, the OXT system in the hypothalamo-neurohypophysial and hypothalamo-spinal pathway was surveyed using a rat neuropathic pain model induced by partial sciatic nerve ligation (PSL). In the present study, we used transgenic rats expressing an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In a neuropathic pain model, mechanical allodynia was observed, and glial cell activation was also confirmed via immunohistochemistry. In this neuropathic pain model, a significant increase in the OXT-mRFP1 expression was observed in the PP, the SON, mPVN, and pPVN. Furthermore, OXT-mRFP1 granules with positive fluorescent reaction were remarkably increased in laminae I and II of the ipsilateral dorsal horn. Although the plasma concentrations of OXT did not significantly change, a significant increase of the mRNA levels of OXT and mRFP1 in the SON, mPVN, and pPVN were observed. These results suggest that neuropathic pain induced by PSL upregulates hypothalamic OXT synthesis and transportation to the OXTergic axon terminals in the PP and spinal cord.

Is Hypothalamic Oxytocin Dispensable for Parturition?

Is Hypothalamic Oxytocin Dispensable for Parturition?

Environmental enrichment enhances conditioned place preference to ethanol via an oxytocinergic-dependent mechanism in male mice

Environmental conditions, such as stress and environmental enrichment (EE), influence predisposition to alcohol use/abuse; however, the underlying mechanisms remain unknown. To assess the effect of environmental conditions on the initial rewarding effects of alcohol, we examined conditioned place-preference (CPP) to alcohol following exposure to EE in mice. Since social context is a major factor contributing to initial alcohol-drinking, we also assessed the impact of EE on the levels of the “social neuropeptide” oxytocin (OT) and its receptor, OTR. Finally, we assessed the effect of pharmacological manipulations of the oxytocinergic system on EE-induced alcohol CPP. While EE increased sociability and reduced anxiety-like behaviors, it caused a ∼3.5-fold increase in alcohol reward compared to controls. EE triggered profound neuroadaptations of the oxytocinergic system; it increased hypothalamic OT levels and decreased OTR binding in the prefrontal cortex and olfactory nuclei of the brain. Repeated administration of the OT analogue carbetocin (6.4 mg/kg/day) mimicked the behavioral effects of EE on ethanol CPP and induced similar brain region-specific alterations of OTR binding as those observed following EE. Conversely, repeated administration of the OTR antagonist L,369–899 (5 mg/kg/day) during EE exposure, but not during the acquisition of alcohol CPP, reversed the pronounced EE-induced ethanol rewarding effect. These results demonstrate for the first time, a stimulatory effect of environmental enrichment exposure on alcohol reward via an oxytocinergic-dependent mechanism, which may predispose to alcohol abuse. This study offers a unique prospective on the neurobiological understanding of the initial stages of alcohol use/misuse driven by complex environmental-social interplay.

Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice

Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT.

Oxytocin Release during the Meditation of Altruism and Appreciation (Arigato-Zen)

A number of modern researchers have studied the relationship between religion and health. In every religious tradition, virtues such as self-sacrifice, altruism, and appreciation have been considered quite essential. Arigato-Zen (AZ) (Gratitude Zen) is an easy and simple voice-meditation developed by Dr. Machida, which motivates the feeling of altruism and appreciation. By performing AZ, one is able to cleanse the negative subconscious memories that underlie problematic phenomena. Hypothalamic oxytocin (OT) plays an important role in the ability to form social attachments, including parental care and pair bonding. It has been shown that social interaction is important to adapt to our daily life stress via the OT expression. It is hypothesized that OT is stimulated via the AZ meditation of altruism and appreciation. Using saliva samples, OT levels were measured in 32 participants before and after AZ. Salivary OT levels were significantly increased after AZ from 66.3 ± 6.7 pg/ml to 90.6 ± 18.7 pg/mL (M ± SE, n = 32, p = 0.028). AZ practice is a quite unique type of meditation, which combines voice-vibration system and traditional Zen meditation in order to synergistically stimulate OT system.

Emotion recognition associated with polymorphism in oxytocinergic pathway gene ARNT2.

The ability to correctly understand the emotional expression of another person is essential for social relationships and appears to be a partly inherited trait. The neuropeptides oxytocin and vasopressin have been shown to influence this ability as well as face processing in humans. Here, recognition of the emotional content of faces and voices, separately and combined, was investigated in 492 subjects, genotyped for 25 single nucleotide polymorphisms (SNPs) in eight genes encoding proteins important for oxytocin and vasopressin neurotransmission. The SNP rs4778599 in the gene encoding aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a transcription factor that participates in the development of hypothalamic oxytocin and vasopressin neurons, showed an association that survived correction for multiple testing with emotion recognition of audio–visual stimuli in women (n = 309). This study demonstrates evidence for an association that further expands previous findings of oxytocin and vasopressin involvement in emotion recognition.

Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice.

Social stress has deteriorating effects on various psychiatric diseases. In animal models, exposure to socially dominant conspecifics (i.e., social defeat stress) evokes a species-specific defeat posture via unknown mechanisms. Oxytocin neurons have been shown to be activated by stressful stimuli and to have prosocial and anxiolytic actions. The roles of oxytocin during social defeat stress remain unclear. Expression of c-Fos, a marker of neuronal activation, in oxytocin neurons and in oxytocin receptor‒expressing neurons was investigated in mice. The projection of oxytocin neurons was examined with an anterograde viral tracer, which induces selective expression of membrane-targeted palmitoylated green fluorescent protein in oxytocin neurons. Defensive behaviors during double exposure to social defeat stress in oxytocin receptor‒deficient mice were analyzed. After social defeat stress, expression of c-Fos protein was increased in oxytocin neurons of the bed nucleus of the stria terminalis, supraoptic nucleus, and paraventricular hypothalamic nucleus. Expression of c-Fos protein was also increased in oxytocin receptor‒expressing neurons of brain regions, including the ventrolateral part of the ventromedial hypothalamus and ventrolateral periaqueductal gray. Projecting fibers from paraventricular hypothalamic oxytocin neurons were found in the ventrolateral part of the ventromedial hypothalamus and in the ventrolateral periaqueductal gray. Oxytocin receptor‒deficient mice showed reduced defeat posture during the second social defeat stress. These findings suggest that social defeat stress activates oxytocin-oxytocin receptor systems, and the findings are consistent with the view that activation of the oxytocin receptor in brain regions, including the ventrolateral part of the ventromedial hypothalamus and the ventrolateral periaqueductal gray, facilitates social defeat posture.

Role of Oxytocin in Prolactin Secretion during Late Pregnancy

Background/Aims: During late pregnancy, the blockade of progesterone action by mifepristone (Mp) treatment induces a dopaminergic tone fall that enables naloxone (NAL) administration to release pituitary prolactin (PRL). We determined whether oxytocin (OT), which stimulates PRL secretion acting directly on anterior pituitary lactotrophs, mediates the stimulatory action of Mp and NAL on PRL secretion during late pregnancy. Methods: On day 19 of pregnancy, circulating and pituitary OT and PRL levels were measured by radioimmunoassay, 10, 20, and 30 min after NAL (given at 17:30 h) in rats pretreated with Mp (at 08:00 h). Pituitary OT receptor (OTR) expression in Mp-treated rats was evaluated by RT-PCR. Activation of OT neurons in Mp-NAL-treated rats was measured counting double immunoreactive neurons for Fos and OT (Fos-OT-ir) in supraoptic nuclei (SON), and medial (PaMM) and lateral magnocellular divisions of paraventricular nuclei. Results: Elevated serum OT and decreased pituitary OT were observed 10 min after NAL administration in both vehicle- and Mp-treated rats. This PRL increase was prevented by previous i.p. administration of an OTR antagonist, but intracerebroventricular OT administration was ineffective. Mp increased pituitary OTR expression at 18:00 h. Only Mp-NAL increased Fos-OT-ir neurons in the PaMM and SON. Conclusions: These findings suggest that PRL secretion induced by Mp-NAL treatment is preceded by OT release. These results, together with the activation of hypothalamic OT neurons and the higher expression of pituitary OTR, support the hypothesis that, during late pregnancy, OT may act at the pituitary level to facilitate PRL secretion if the inhibitory action of progesterone is blocked.