Oxytocin Attenuates the Stress-Induced Reinstatement of Alcohol-Seeking in Male Rats: Role of the Central Amygdala

Factors such as stress and anxiety often contribute to alcohol-dependent behavior and can trigger a relapse of alcohol addiction and use. Therefore, it is important to investigate potential pharmacological interventions that may alleviate the influence of stress on addiction-related behaviors. Previous studies have demonstrated that the neuropeptide oxytocin has promising anxiolytic potential in mammals and may offer a pharmacological target to diminish the emotional impact on reinstatement of alcohol-seeking. The purpose of the present study was to investigate the effect of oxytocin on stress-induced alcohol relapse and identify a neural structure mediating this effect through the use of an ethanol self-administration and yohimbine-induced reinstatement paradigm. While yohimbine administration resulted in the reinstatement of ethanol-seeking behavior, the concurrent administration of yohimbine and oxytocin attenuated this effect, suggesting that oxytocin may disrupt stress-induced ethanol-seeking behavior. The central amygdala (CeA) is a structure that drives emotional responses and robustly expresses oxytocin receptors. Intra-CeA oxytocin similarly attenuated the yohimbine-induced reinstatement of ethanol-seeking behavior. These results demonstrate that oxytocin has the potential to attenuate stress-induced relapse into ethanol-seeking behavior, and that this mechanism occurs specifically within the central amygdala.

Clinical features of labor and morphological aspects of the myometrium receptor profile in obese women

BACKGROUND: Obesity is currently considered as one of the most significant social chronic diseases. It has been proven that obese pregnant women are more likely than women with normal body weight to experience complications of pregnancy and labor. The most frequent complications of labor in obese women are weakness and discoordination, which are probably associated with a decrease in the sensitivity of the myometrium to oxytocin, due to suppression of oxytocin receptor expression. AIM: The aim of this study was to explore the clinical features of labor and morphological aspects of the myometrium receptor apparatus in obese women. MATERIALS AND METHODS: We performed a prospective assessment of labor activity in women with obesity, with a combination of obesity and gestational diabetes mellitus and in healthy women. We also conducted a morphological study of myometrium biopsies obtained during cesarean section. RESULTS: Obese patients are more likely to experience various complications of pregnancy and labor, which is the reason for the higher frequency of operative delivery. Patients with obesity showed lower expression of oxytocin receptors in the lower segment of the uterus, which, apparently, is the cause of abnormal contractility of the myometrium during labor and the lack of effect from drug correction of this condition. CONCLUSIONS: The presence of obesity in women before pregnancy contributes to frequent complications of pregnancy and labor, abnormal uterine contractility related to the decreased oxytocin receptor expression, and a high incidence of surgical delivery.

Optimal Method for Disulfide Bond Closure in the Synthesis of Atosiban—Antagonist of Oxytocin Receptors

This work is devoted to the large-scale solid-phase synthesis (SPS) of Atosiban, Mpa1-D-Tyr(OEt)-Ile-Thr-Asn-Cys6-Pro-Orn-Gly-NH2 cyclic 1,6 disulfide, the only clinically used oxytocin receptor antagonist. The conditions have been selected for the closure of the disulfide bond (S–S) in the Atosiban molecule both in the solution and solid phase with the minimal formation of by-products. A comparative assessment of the formation of the S–S bond was carried out under various conditions. The formation of by-products during the closure of the disulfide bond has been studied both in solution and on the polymer support. The developed technique allows for the synthesis of Atosiban on an enlarged scale (10–20 mmol) involving the cyclization of a protected intermediate with the formation of the S–S bond during solid-phase synthesis with the minimal formation of by-products.

Postpartum haemorrhage and synthetic oxytocin dilutions in labour

This study investigated postpartum haemorrhage and historic oxytocin usage, because haemorrhage rates are rising. During the evolution of practice from intravenous bovine post-pituitary extract to synthetic oxytocin, experimental interventions had produced improved outcomes in certain cases and the postpartum haemorrhage rate was low. In this study, current synthetic oxytocin regimes from across the UK were compared with the 1977 (unchanged) licensed instructions for infusion. As a result of the pain-inducing properties of synthetic oxytocin, epidural analgesia prior to infusion is now standard for unlicensed regimes, adding complexity to intrapartum care and greater risks of complex births, as the fetus may be adversely affected by epidural drugs and acidosis. Unlicensed synthetic oxytocin dilutions and increments, the desensitising of oxytocin receptors, and unmeasured error factors in infusion pumps affect labour progress and outcomes. Today's rates of postpartum haemorrhage are associated with these changes to obstetric practice. Failure to inform women of intended unlicensed practices with synthetic oxytocin, or obtain consent for such, or offer licensed practice as standard constitutes neglect of the legal obligations outlined for doctors and midwives by professional Codes of Practice, intended to protect patients from predictable dangers.

Sexual Experience Induces the Expression of Gastrin-Releasing Peptide and Oxytocin Receptors in the Spinal Ejaculation Generator in Rats

Male sexual function in mammals is controlled by the brain neural circuits and the spinal cord centers located in the lamina X of the lumbar spinal cord (L3–L4). Recently, we reported that hypothalamic oxytocin neurons project to the lumbar spinal cord to activate the neurons located in the dorsal lamina X of the lumbar spinal cord (dXL) via oxytocin receptors, thereby facilitating male sexual activity. Sexual experiences can influence male sexual activity in rats. However, how this experience affects the brain–spinal cord neural circuits underlying male sexual activity remains unknown. Focusing on dXL neurons that are innervated by hypothalamic oxytocinergic neurons controlling male sexual function, we examined whether sexual experience affects such neural circuits. We found that >50% of dXL neurons were activated in the first ejaculation group and ~30% in the control and intromission groups in sexually naïve males. In contrast, in sexually experienced males, ~50% of dXL neurons were activated in both the intromission and ejaculation groups, compared to ~30% in the control group. Furthermore, sexual experience induced expressions of gastrin-releasing peptide and oxytocin receptors in the lumbar spinal cord. This is the first demonstration of the effects of sexual experience on molecular expressions in the neural circuits controlling male sexual activity in the spinal cord.

Oxytocin: much more than childbirth and milk letdown

This commentary deals with the new observations that dendritic cell (DC) oxytocin receptors play a role in the inflammatory response generated in murine animal models of colitis. The overview provides a context of the discovery of oxytocin (OT), its chemical synthesis and the cell biology of its neurohypophysial synthesis and secretion. This perspective provides insight and raises questions to be answered related to the impact of OT in the gastrointestinal tract and to further the exploration of OT as a potentially locally synthesised regulator of intestinal inflammatory pathophysiology.

Oxytocin and Pregnancy

Oxytocin, an important neuropeptide, exerts a wide influence on the central nervous system and the peripheral tissues. In the central nervous system, the oxytocin gene expression is mainly shown to be present in neurons in the hypothalamic paraventricular and supraoptic nuclei. Oxytocin gene also transcribes in the peripheral tissues such as uterus, placenta, and amnion. Oxytocin receptors can be founded in many tissues in humans, like the uterine, ovary, testis, kidney, and so on. And just in the same tissue, due to the variation of physiology factors, the amount of oxytocin changes a lot. Oxytocin secretion is closely linked with pregnancy advancing. During labor, the contractions of uterine smooth muscles and oxytocin secretion are inseparable. Moreover, oxytocin is also responsible for stimulating milk ejection after parturition. Oxytocin is associated with many diseases. Poor regulation of oxytocin may cause postpartum depression and infantile autism. In terms of physiology, fatal heart failure and gestational hypertension are concerned with oxytocin level. In this chapter, we will discuss the oxytocin in pregnancy as well as its clinical applications.

Oxytocin Signaling Acts as a Marker for Environmental Stressors in Zebrafish

The oxytocin system plays a role in stress responses and behavior modulation. However, the effects of oxytocin signaling on stress adaptation remain unclear. Here, we demonstrated the roles of oxytocin signaling as a biomarker under stress conditions in the peripheral tissues (the gills) and central nervous system (the brain). All the environmental stressors downregulated the expression of oxytocin receptors in the gills, and the alteration of the expression of oxytocin receptors was also found in the brain after the acidic (AC) and high-ammonia (HA) treatments. The number of oxytocin neurons was increased after double-deionized (DI) treatment. By transgenic line, Tg(oxtl:EGFP), we also investigated the projections of oxytocin neurons and found oxytocin axon innervations in various nuclei that might regulate the anxiety levels and aggressiveness of adult zebrafish under different environmental stresses. The oxytocin system integrates physiological responses and behavioral outcomes to ensure environmental adaptation in adult zebrafish. Our study provides insight into oxytocin signaling as a stress indicator upon environmental stressors.

Oxytocin receptors influence the development and maintenance of social behavior in zebrafish (Danio rerio).

Zebrafish are highly social teleost fish and an excellent model to study social behavior. The neuropeptide Oxytocin is associated different social behaviors as well as disorders resulting in social impairment like autism spectrum disorder. However, how Oxytocin receptor signaling affects the development and expression kinetics of social behavior is not known. In this study we investigated the role of the two oxytocin receptors, Oxtr and Oxtrl, in the development and maintenance of social preference and shoaling behavior in 2- to 8-week-old zebrafish. Using CRISPR/Cas9 mediated oxtr and oxtrl knock-out fish, we found that the development of social preference is accelerated if one of the Oxytocin receptors is knocked-out and that the knock-out fish reach significantly higher levels of social preference. Moreover, oxtr-/- fish showed impairments in the maintenance of social preference. Social isolation prior to testing led to impaired maintenance of social preference in both wild-type and oxtr and oxtrl knock-out fish. Knocking-out one of the Oxytocin receptors also led to increased group spacing and reduced polarization in a 20-fish shoal at 8 weeks post fertilization, but not at 4. These results show that the development and maintenance of social behavior is influenced by the Oxytocin receptors and that the effects are not just pro- or antisocial, but dependent on both the age and social context of the fish.