Peripheral Release Of Oxytocin Research Articles

The endogenous oxytocin after manipulative osteopathic treatment in full-term pregnant women.

The aim of this study is to assess whether the touch of osteopathic manipulative treatment (OMT) can affect the endogenous production of oxytocin in full-term pregnant women and the assessment of well-being following the treatment. In this study have been enrolled 57 pregnant women at full-term pregnancy (37th-41st week) for evaluation of the concentration of salivary oxytocin 2 minutes before and 2 minutes after a single session of OMT by an osteopath lasting for 30 minutes. Pre-OMT and post-OMT saliva samples were collected with the use of Salivette® salivary swabs. 7 salivary swabs were excluded from the analysis. 50 samples were analyzed with an appropriate ELISA kit. The mean OT salivary concentration pre-OMT was 89.98±16.39, and post-OMT was 100.60±19.13 tends to increase with p=0.0000051. In multivariate analysis, two subgroups show interesting data in the mean difference in OT salivary concentration post-OMT: women with painful contractions (p=0.06) and women under 35 years (p=0.09). The results of this study demonstrate that the effectiveness of OMT-increasing endogenous oxytocin is statistically significant in full-term pregnant women. The sensation of well-being found in most women indicates that there has been a predominantly central rather than peripheral oxytocin release after OMT.

Exploring associations between postpartum depression and oxytocin levels in cerebrospinal fluid, plasma and saliva

BackgroundPostpartum depression (PPD) is a serious mental health concern affecting approximately 17.22 % of new mothers worldwide. In addition to its obstetric effects, oxytocin (OXT) has also been considered to play a role in PPD. However, most previous studies exploring associations between PPD and OXT levels focus on easier accessible compartments such as blood or saliva. Study aimTo explore the possible association between PPD and OXT levels, and to assess the interaction between peripheral secretion and central release of OXT. MethodsIn this study, we prospectively measured OXT concentrations in cerebrospinal fluid (CSF), plasma and saliva of 94 women with elective cesarean section by enzyme-linked immunosorbent assay (ELISA) kits. The participants were divided into the PPD group if the score of Edinburgh Postpartum Depression Scale (EPDS) ≥ 10 at 3 months postpartum, otherwise into the non-PPD (nPPD) group. ResultsThe incidence of PPD was 30.85 %. OXT concentrations in CSF (r = −0.518, p < 0.001), plasma (r = −0.240, p = 0.020) and saliva (r = −0.263, p = 0.010) were negatively correlated with EPDS score, and were valuable for the prediction of PPD, with AUC and 95%CI of 0.890 (0.809–0.945), 0.683 (0.579–0.775) and 0.699 (0.596–0.790), respectively. Moreover, OXT concentrations in plasma (r = 0.407, p < 0.001) and saliva (r = 0.624, p < 0.001) were positively correlated with CSF OXT concentrations. LimitationsOnly full-term pregnant women undergoing elective cesarean section were included in this study, which may affect study generalizability. ConclusionsThe central and peripheral release of OXT is coordinated, and OXT level measured prenatally in CSF, plasma, or saliva is valuable for the prediction of PPD.

Plasma oxytocin is modulated by mental training, but does not mediate its stress-buffering effect

Based on its role in social processing and stress, oxytocin has been suggested to mediate stress reduction of socio-affective, compassion-based mental training. We tested this hypothesis in the ReSource Project, a 9-month longitudinal mental training study. Participants practiced three different types of mental training, targeting either attentional abilities (Presence Module), socio-affective or socio-cognitive abilities (Affect and Perspective Modules). We investigated plasma oxytocin levels, and their link to cortisol and subjective reactivity to acute psychosocial stress as a function of previous mental training (n = 313). In a subsample (n = 113), to better understand oxytocin’s involvement in the effects of socio-affective training, we explored oxytocin, cortisol and subjective experiential responses to a single Loving-kindness Meditation (LKM) conducted after three months of Affect training (versus rest without prior training). We found that, independent of mental training, stress triggered acute oxytocin release. Following a single LKM, however, acute oxytocin release was unaffected. Training effects were only found in overall oxytocin release during both, stress and LKM. Compared to no training, 3-month compassion-based Affect training decreased overall oxytocin levels in the context of psychosocial stress, but increased overall oxytocin levels during LKM. Training-induced changes in overall oxytocin were unrelated to cortisol and subjective stress reactivity. Based on Quintana and Guastella's (2020) theory of oxytocin as an allostatic hormone with anticipatory properties, we interpret training-induced changes in overall oxytocin levels as alterations in the anticipated emotional relevance of specific events. After training socio-affective skills for three months, the stressful situation may have lost its emotional saliency, whereas the meditation technique itself gained emotional relevance. We conclude that changes in peripheral oxytocin release do not mediate stress reduction after mental training, and encourage the investigation of an allostatic concept of oxytocin in future research.

Chapter 3 - Central and peripheral release of oxytocin: Relevance of neuroendocrine and neurotransmitter actions for physiology and behavior

The hypothalamic neuropeptide oxytocin (OT) is critically involved in the modulation of socio-emotional behavior, sexual competence, and pain perception and anticipation. While intracellular signaling of OT and its receptor (OTR), as well as the functional connectivity of hypothalamic and extra-hypothalamic OT projections, have been recently explored, it remains elusive how one single molecule has pleotropic effects from cell proliferation all the way to modulation of complex cognitive processes. Moreover, there are astonishing species-dependent differences in the way OT regulates various sensory modalities such as touch, olfaction, and vision, which can be explained by differences in OTR expression in brain regions processing sensory information. Recent research highlights a small subpopulation of OT-synthesizing cells, namely, parvocellular cells, which merely constitute 1% of the total number of OT cells but act as "master cells' that regulate the activity of the entire OT system. In this chapter, we summarize the latest advances in the field of OT research with a particular focus on differences between rodents, monkeys and humans and highlight the main differences between OT and its "sister" peptide arginine-vasopressin, which often exerts opposite effects on physiology and behavior.

Reconstruction of the Hypothalamo-Neurohypophysial System and Functional Dissection of Magnocellular Oxytocin Neurons in the Brain

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.

Kisspeptin Regulation of Oxytocin Neuron Activity in Late Pregnancy

Oxytocin is secreted from the posterior pituitary gland by oxytocin neurons to trigger uterine contractions during birth. We have recently shown that the oxytocin neuron firing rate increases in response to intracerebroventricular (ICV) kisspeptin only in late‐pregnant rats. Furthermore, the kisspeptin projection from the periventricular nucleus of the hypothalamus (PeN) to the perinuclear zone (PNZ) surrounding the supraoptic nucleus (SON) increases in late pregnancy. This study aimed to determine the site and mechanism of central kisspeptin activation of oxytocin neuron activity in late pregnant rats. First, in vivo extracellular single unit recordings were made from SON neurons in urethane‐anaesthetised non‐pregnant and late‐pregnant rats during microdialysis application of kisspeptin (100 μM in the dialysate) into the SON. Intra‐SON kisspeptin consistently increased the firing rate of oxytocin neurons in late‐pregnant rats but not in non‐pregnant rats. Two‐way repeated measures (RM) ANOVA revealed a significant interaction between REPRODUCTIVE STATUS and TIME (F(6,88) = 10.31, p &lt; 0.001); post hoc all pairwise Holm‐Sidak tests revealed a significant increase in firing rate in late‐pregnant rats at 30 (p &lt; 0.05), 40, 50 and 60 minutes (all p &lt; 0.001 versus pre‐kisspeptin), and a significantly higher firing rate than in time‐matched recordings from non‐pregnant rats at 50 and 60 minutes (p &lt; 0.05).Then, to examine whether excitatory effects of central kisspeptin emerges directly within the SON and paraventricular nucleus (PVN) containing oxytocin neurons, we performed single label diaminobenzidine (DAB) immunostaining against phosphorylated extracellular regulated kinase (pERK), a second messenger activated by kisspeptin. ICV cannulae were implanted on day 13 or 14‐pregnant and non‐pregnant rats and one week later, day 21 pregnant and non‐pregnant rats were perfused 15 min after ICV administration of kisspeptin (2 μg/2 μl) or vehicle under pentobarbital anaesthesia. ICV kispeptin injection did not alter pERK expression in the SON or PVN. Two‐way RM ANOVA revealed a significant effect of REPRODUCTIVE STATUS (F(1,28) = 4.78, p = 0.03) but no significant effect of TREATMENT (kisspeptin/vehicle) (F(1,28) = 0.04, p = 0.82) and no REPRODUCTIVE STATUS X TREATMENT interaction (F(1,28) = 0.81, p = 0.37 ) in the SON. There was no significant effect of REPRODUCTIVE STATUS (F(1,27) = 0.93, p = 0.34, two‐way RM ANOVA) or TREATMENT (F(1,27) = 0.93, p = 0.34) and no REPRODUCTIVE STATUS X TREATMENT interaction (F(1,27) = 0.29, p = 0.59) in the PVN. Similarly, there was no significant effect of REPRODUCTIVE STATUS (F(1,27) = 2.28, p = 0.14, two‐way RM ANOVA) or TREATMENT (F(1,27) = 0.28, p = 0.59) and no REPRODUCTIVE STATUS X TREATMENT interaction (F(1,27) = 0.07, p = 0.78) in the magnocellular division of PVN. Hence, it appears that kisspeptin excites oxytocin neurons at the end of pregnancy by a presynaptic action at local nerve terminals to stimulate peripheral oxytocin release and so might contribute to oxytocin neuron activation for parturition.

Chemogenetic activation of oxytocin neurons: Temporal dynamics, hormonal release, and behavioral consequences

Chemogenetics provides cell type-specific remote control of neuronal activity. Here, we describe the application of chemogenetics used to specifically activate oxytocin (OT) neurons as representatives of a unique class of neuroendocrine cells. We injected recombinant adeno-associated vectors, driving the stimulatory subunit hM3Dq of a modified human muscarinic receptor into the rat hypothalamus to achieve cell type-specific expression in OT neurons. As chemogenetic activation of OT neurons has not been reported, we provide systematic analysis of the temporal dynamics of OT neuronal responses in vivo by monitoring calcium fluctuations in OT neurons, and intracerebral as well as peripheral release of OT. We further provide evidence for the efficiency of chemogenetic manipulation at behavioral levels, demonstrating that evoked activation of OT neurons leads to social motivation and anxiolysis. Altogether, our results will be profitable for researchers working on the physiology of neuroendocrine systems, peptidergic modulation of behaviors and translational psychiatry.

Breastfeeding behavior and oxytocin related genes

The peripheral release of oxytocin has been identified during parturition, lactation, and sexual function in humans. Recent studies have shown that oxytocin is also related to parenting style and sensitive responsiveness towards the child. Few studies have analysed the relationship between variation in oxytocin related genes and breastfeeding behavior. In this study we tested for associations between polymorphisms in the OXT and OXTR genes and breastfeeding duration for the first child and average for all children. The sample comprised 724 women who had been mothers participating in the Murcia Twin Registry, in Spain. Preliminary results points to an association of some polymorphisms (especially in the OXTR gene) and breastfeeding. Future studies should replicate these analyses.

Central and peripheral release of oxytocin following chronic homotypic stress in rats

Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Centrally released oxytocin has anxiolytic and anti-stress effects. We have recently shown that impaired gastric and colonic motility observed in acute restraint stress was restored following repeated restraint stress for 5 consecutive days (chronic homotypic stress) in mice and rats. Chronic homotypic stress upregulates oxytocin mRNA expression and downregulates corticotrophin-releasing factor (CRF) mRNA expression at the hypothalamus. However, it still remains unclear whether stress responses induced by chronic homotypic stress are accompanied by the central or peripheral release of oxytocin. Adult male SD rats were chronically implanted with microdialysis probes at the hypothalamic paraventricular nucleus (PVN) and jugular vein catheters. Microdialysis and blood sampling were performed following 1st, 3rd and 5th of chronic homotypic stress. Oxytocin levels in the dialysates and plasma were measured by radioimmunoassay (RIA). On day 1 of chronic homotypic stress, oxytocin release was slightly, but not significantly, increased in the PVN and plasma. Oxytocin release was significantly increased in the PVN on day 3 (12.7±1.3pg/sample, n=5, P<0.05) and day 5 (28.2±2.4pg/sample, n=5, P<0.05) from basal (6.9±1.8pg/sample, n=5). In contrast, there were no significant changes observed in the plasma on day 3 and day 5. This suggests that central, but not peripheral, release of oxytocin plays an important role in response to chronic homotypic stress in rats.

Evidence of Dysregulated Peripheral Oxytocin Release Among Depressed Women

Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female reproductive function. Animal research indicates that central oxytocin facilitates adaptive social attachments and modulates stress and anxiety responses. Major depression is prevalent among postpubertal females, and is associated with perturbations in social attachments, dysregulation of the hypothalamic-pituitary-adrenal stress axis, and elevated levels of anxiety. Thus, depressed women may be at risk to display oxytocin dysregulation. The current study was developed to compare patterns of peripheral oxytocin release exhibited by depressed and nondepressed women. Currently depressed (N = 17) and never-depressed (N = 17) women participated in a laboratory protocol designed to stimulate, measure, and compare peripheral oxytocin release in response to two tasks: an affiliation-focused Guided Imagery task and a Speech Stress task. Intermittent blood samples were drawn over the course of two, 1-hour sessions including 20-minute baseline, 10-minute task, and 30-minute recovery periods. The 10-minute laboratory tasks did not induce identifiable, acute changes in peripheral oxytocin. However, as compared with nondepressed controls, depressed women displayed greater variability in pulsatile oxytocin release over the course of both 1-hour sessions, and greater oxytocin concentrations during the 1-hour affiliation-focused imagery session. Oxytocin concentrations obtained during the imagery session were also associated with greater symptoms of depression, anxiety, and interpersonal dysfunction. Depressed women are more likely than controls to display a dysregulated pattern of peripheral oxytocin release. Further research is warranted to elucidate the clinical significance of peripheral oxytocin release in both depressed and nondepressed women.

Neural nitric oxide gene inactivation affects the release profile of oxytocin into the blood in response to forced swimming

This study was undertaken to examine the importance of nitric oxide (NO) generated by the neural isoform of the nitric oxide synthase (nNOS) on the activity of the hypothalamic neurohypophyseal system in neural nitric oxide synthase knock-out (KO) and wild-type (WT) mice under basal conditions and in response to forced swimming. The intensity of the hybridisation signal for vasopressin (AVP) in the hypothalamic supraoptic nucleus (SON) was significantly higher in KO mice when compared with WT, whereas oxytocin (OXT) basal mRNA levels were similar in both groups. Although the basal peripheral release of AVP and OXT was equivalent in both genotypes, we observed in KO mice a significant drop of AVP and OXT plasma values 15 min after stressor onset and a robust increase in the OXT plasma concentration at 60 min. These findings suggest that in the male mouse, NO inhibits AVP gene transcription in magnocellular neurones of the SON and collaborates in maintaining constant AVP and OXT plasma levels following acute stressor exposure, exerting a bimodal regulatory action on OXT secretion. We conclude that NO is involved in the regulation of magnocellular neurones of the SON, and it is preferentially implicated in the attenuation of the peripheral release of OXT induced by acute stressor exposure.

Presynaptic actions of endocannabinoids mediate α-MSH-induced inhibition of oxytocin cells

We recently showed that central injections of alpha-melanocyte-stimulating hormone (alpha-MSH) inhibits oxytocin cells and reduces peripheral release of oxytocin, but induces oxytocin release from dendrites. Dendritic oxytocin release can be triggered by agents that mobilize intracellular calcium. Oxytocin, like alpha-MSH, mobilizes intracellular calcium stores in oxytocin cells and triggers presynaptic inhibition of afferent inputs that is mediated by cannabinoids. We hypothesized that this mechanism might underlie the inhibitory effects of alpha-MSH. To test this, we recorded extracellularly from identified oxytocin and vasopressin cells in the anesthetized rat supraoptic nucleus (SON). Retrodialysis of a CB1 cannabinoid receptor antagonist to the SON blocked the inhibitory effects of intracerebroventricular injections of alpha-MSH on the spontaneous activity of oxytocin cells. We then monitored synaptically mediated responses of SON cells to stimulation of the organum vasculosum of the lamina terminalis (OVLT); this evoked a mixed response comprising an inhibitory component mediated by GABA and an excitatory component mediated by glutamate, as identified by the effects of bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione applied to the SON by retrodialysis. Application of CB1 receptor agonists to the SON attenuated the excitatory effects of OVLT stimulation in both oxytocin and vasopressin cells, whereas alpha-MSH attenuated the responses of oxytocin cells only. Thus alpha-MSH can act as a "switch"; it triggers oxytocin release centrally, but at the same time through initiating endocannabinoid production in oxytocin cells inhibits their electrical activity and hence, peripheral secretion.

Neural pathways controlling central and peripheral oxytocin release during stress.

Oxytocin is released from the pituitary gland in response to a variety of stressful stimuli, including noxious stimuli, conditioned fear and exposure to novel environments. These responses are believed to be mediated, at least in part, by noradrenergic projections from the medulla oblongata, and some of these noradrenergic neurones also contain prolactin-releasing peptide (PrRP). Central administration of either PrRP or noradrenaline stimulates oxytocin secretion into the circulation. Stressful stimuli activate PrRP-containing noradrenergic neurones in the medulla oblongata, and it is thus possible that PrRP/noradrenergic projections to the hypothalamus mediate oxytocin responses to stressful stimuli. Here, the roles of brainstem PrRP/noradrenergic projections to the hypothalamus in oxytocin responses to different kinds of stressful stimuli are reviewed, with a particular emphasis on conditioned fear. Roles of dendritic oxytocin release during stress and metabolic factors affecting stress pathways are also discussed.

Neuronal, glial and synaptic remodeling in the adult hypothalamus: functional consequences and role of cell surface and extracellular matrix adhesion molecules

The adult hypothalamo-neurohypophysial system (HNS) undergoes activity-dependent morphological plasticity which modifies astrocytic coverage of its oxytocinergic neurons and their synaptic inputs. Thus, during physiological conditions that enhance central and peripheral release of oxytocin (OT), adjacent somata and dendrites of OT neurons become extensively juxtaposed, without intervening astrocytic processes and receive an increased number of synapses. The morphological changes occur within a few hours and are reversible with termination of stimulation. The reduced astrocytic coverage has direct functional consequences since it modifies extracellular ionic homeostasis, synaptic transmission, and the size and geometry of the extracellular space. It also contributes indirectly to neuronal function by permitting formation of synapses on neuronal surfaces freed of astrocytic processes. Overall, such remodeling is expected to potentiate activated neuronal firing, especially in clusters of tightly packed neurons, an anatomical arrangement characterizing OT neurons. This plasticity connotes dynamic cell interactions that must bring into play cell surface and extracellular matrix adhesive proteins like those intervening in developing neuronal systems undergoing neuronal–glial and synaptogenic transformations. It is worth noting, therefore, that adult HNS neurons and glia continue to express such molecules, including polysialic acid (PSA)-enriched neural cell adhesion molecule (PSA-NCAM) and the glycoprotein, tenascin-C. PSA is a large, complex sugar on the extracellular domain of NCAM considered a negative regulator of adhesion; it occurs in large amounts on the surfaces of HNS neurons and astrocytes. Tenascin-C, on the other hand, possesses adhesive and repulsive properties; it is secreted by HNS astrocytes and occurs in extracellular spaces and on cell surfaces after interaction with appropriate ligands. These molecules have been considered permissive factors for morphological plasticity. However, because of their localization and inherent properties, they may also serve to modulate the extracellular environment and in consequence, synaptic and volume transmission in a system in which the extracellular compartment is constantly being modified.

Chapter 12 Involvement of the brain oxytocin system in stress coping: interactions with the hypothalamo-pituitary-adrenal axis

In response to various ethologically relevant stressors, oxytocin is released not only from neurohypophysial terminals into the blood, but also within distinct brain regions, for example the hypothalamic supraoptic and paraventricular nuclei, the septum and the amygdala in dependence on the quality and intensity of the stressor. Thus, oxytocin secretory activity may accompany the response of the hypothalamo-pituitary-adrenal (HPA) axis to a given stressor. In the present chapter, I try to summarize our efforts to reveal the physiological significance of intracerebrally released oxytocin in rats with respect to the regulation of the HPA axis under basal and stress conditions as well as with respect to behavioural stress responses. The effects of oxytocin appear to depend on the brain region studied and the state of activity of the animal (basal versus stress). In order to reveal interactions between the oxytocin system and the HPA axis, preliminary results are presented pointing towards a differential action of glucocorticoids on intracerebral and peripheral oxytocin release.

Physiological regulation of maternal behavior in heifers: roles of genital stimulation, intracerebral oxytocin release, and ovarian steroids.

We tested the hypotheses that 1) epidural anesthesia at parturition would block both peripheral and central release of oxytocin and eliminate the development of maternal behavior in primiparous heifers and 2) estradiol priming, genital stimulation, and appropriate neonatal stimuli would induce maternal behavior in nulliparous heifers. In experiment 1, primiparous crossbred heifers (n = 13) with cannulas in the third cerebroventricle (IIIV) were assigned randomly to receive epidural treatments of saline (SAL; n = 6) or lidocaine HCl (EPI; n = 7) at the onset of labor induced between Days 270 and 280 of gestation. Epidural anesthesia blocked (P < 0.001) both central and peripheral release of oxytocin and markedly reduced (P < 0.05) or eliminated licking behaviors during a 3-h period following parturition as compared with SAL. Following approximately 1 wk of controlled daily suckling, during which calves were permitted access only to the inguinal region of their dams (three times daily for 10 min each time), a second maternal behavior test was performed. Although licking behavior remained markedly reduced (P < 0.001) in the EPI compared with the SAL groups, all heifers accepted their calf at the udder. In experiments 2-4, neither estradiol priming in ovariectomized heifers nor estradiol plus progesterone in intact heifers resulted in an induction of maternal behaviors following genital stimulation and presentation of a neonate wetted with amniotic fluid. Pelvic sensory deficits apparently block oxytocin release and disturb both short-latency and long-term maternal behaviors but do not result ultimately in rejection of the calf. Combinations of hormonal, sensory, olfactory, and visual cues observed previously to induce maternal behavior in nulliparous ewes do not appear adequate for induction of maternal behavior in nulliparous heifers.

Effect of centrally administered opioid receptor agonists on CSF and plasma oxytocin concentrations in dogs.

To measure oxytocin concentrations in blood and CSF following central administration of opioid agonists in dogs. 5 male dogs. In a crossover design, CSF and blood were collected immediately before and 15 and 30 minutes after cisternal administration of D-Ala2, MePhe4, Gly-ol-enkephalin (DAMGO, a mu-receptor agonist); D-Pen, pCl-Phe4, D-Pen5-enkephalin (a delta-receptor agonist); U50488H (a kappa-receptor agonist); morphine; and saline (0.9% NaCl) solution. Plasma oxytocin concentration was significantly increased 15 minutes after administration of DAMGO and 30 minutes after administration of U50488H, compared with concentrations obtained after administration of saline solution. Concentration of oxytocin in CSF was significantly decreased 30 minutes after administration of U50488H, compared with concentration after administration of saline solution. Results suggest that in male dogs, activation of centrally located mu and kappa receptors elicits an overall excitatory effect on neurons that regulate peripheral release of oxytocin, whereas activation of centrally located kappa receptors elicits an overall inhibitory effect on neurons that regulate central release. These results are in contrast to those reported for other species, in which opioids have a pronounced inhibitory effect on release of oxytocin from the neurohypophysis.

Emotional stress triggers intrahypothalamic but not peripheral release of oxytocin in male rats.

Previous experiments have shown that an exposure to defined stressors activates not only the 'classical' endocrine stress response but also the intrahypothalamic and peripheral release of oxytocin. In the present study we investigated the effects of an acute social defeat experience on the release of oxytocin within the hypothalamic supraoptic nucleus, just outside of the supraoptic nucleus toward the midline within the anterior ventro-lateral part of the hypothalamus, and into plasma of adult male rats. Our results demonstrate that emotional stress triggers the release of oxytocin into the extracellular fluid of both the supraoptic nucleus and the anterior ventro-lateral part of the hypothalamus (up to approximately 320% and 170%, respectively). Interestingly, oxytocin release within the latter brain area, which is likely to originate from axons forming the hypothalamo-neurohypophysial tract, was higher in absolute terms than that within the supraoptic nucleus itself, both under basal conditions and in response to social defeat. In contrast to intrahypothalamic release patterns, plasma oxytocin levels remained virtually unchanged upon stressor exposure. This demonstrates that the release of oxytocin within the hypothalamus is triggered by emotional stress. Furthermore, it indicates that under physiological conditions the release of oxytocin from the dendrites and somata upon axon terminals in the neurohypophysis is differentially regulated. Although not yet studied in detail, it may be hypothesized that the spatial and temporal release pattern of oxytocin is controlled by integrative neuronal networks at different brain levels (including hypothalamus and posterior pituitary) to ensure the appropriate involvement of this peptide in the stress response of the animal.

Opioids influence neurohypophysial but not central oxytocin release following direct hyperosmotic stimulation of the supraoptic nucleus in urethane-anaesthetised rats

Microdialysis was used to apply an osmotic stimulus (0.5 M NaCl-aCSF) into both supraoptic nuclei (SON) to investigate the role of endogenous opioid peptides in the control of both central and peripheral oxytocin release in response to this stimulus. There were no differences in central peptide release during direct hyperosmotic stimulation between groups of rats given either vehicle, morphine (5 mg/kg) or naloxone (5 mg/kg) intravenously. Naloxone potentiated oxytocin release into blood; this suggests that endogenous opioid peptides at the level of the neurohypophysis, but not in the SON are important modulators of oxytocin release to this stimulus. However morphine blocked oxytocin release into blood indicative of a central inhibitory action on the firing rate of oxytocin neurones, contrasted with insensitivity to morphine of oxytocin secretion from the dendrites stimulated directly by hyperosmolarity.

An oxytocin receptor antagonist infused into the supraoptic nucleus attenuates intranuclear and peripheral release of oxytocin during suckling in conscious rats

An oxytocin receptor antagonist infused into the supraoptic nucleus attenuates intranuclear and peripheral release of oxytocin during suckling in conscious rats