Oxytocin

Oxytocin (α-Hypophamine) is a mammalian neurohypophysial hormone; its actions are mediated by specific, high-affinity oxytocin receptors; ligand of oxytocin receptor.

References:
[1]. Oxytocin, From Wikipedia

Effects of social deprivation on social and depressive-like behaviors and the numbers of oxytocin expressing neurons in rats.[Pubmed:28377259]

Behav Brain Res. 2017 Jun 15;328:28-38.

Social isolation is a known stressor that negatively impacts the well-being of social species. In rodents, social deprivation experienced either before or after weaning profoundly impacts adult behavioral and neuroendocrine profiles. This study compared the effects of post-natal and post-weaning social deprivation on behavioral profiles and hypothalamic Oxytocin (OT) neurons. Male and female Sprague-Dawley rats were assigned to two post-natal groups, maternally separated (MS) or non-MS. MS pups were separated from their mothers for 4h daily during post-natal days 2-21 while non-MS litters remained undisturbed. Animals were then weaned and assigned to single or group housing conditions (SH/GH). Social behaviors were evaluated two weeks later and at 2-3 months of age, depressive-like behavioral profiles were assessed using the forced swim and sucrose preference tests. Animals were euthanized, and hypothalamic OT neurons were quantified. Post-weaning isolation significantly impacted behavioral profiles, with SH animals displaying more social behaviors than GH animals. SH animals also exhibited more immobility behavior in the forced swim test and a decreased sucrose preference. Effects of sex and MS were relatively limited. Correlation analyses revealed an inverse relationship between the display of antagonistic social behaviors and the numbers of OT cells in the anterior parvicellular division of the paraventricular nucleus (PVNap). There were no correlations between numbers of OT neurons and prosocial or depressive-like behaviors. Our results demonstrate a rapid and persistent disruption of behaviors in SH animals and suggest that some of these effects may be associated with numbers of OT neurons in the PVNap.

Oxytocin treatment in children with Prader-Willi syndrome: A double-blind, placebo-controlled, crossover study.[Pubmed:28371242]

Am J Med Genet A. 2017 May;173(5):1243-1250.

Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder which includes hypothalamic dysfunction, hyperphagia, cognitive and behavioral problems, increased anxiety, and compulsive behaviors. Individuals with PWS have a deficit of Oxytocin producing neurons in the paraventricular nucleus of the hypothalamus. Oxytocin plays a role in regulation of feeding behaviors, social interactions, and emotional reactivity, which are all issues that significantly affect the quality of life for individuals with this syndrome. We performed a double-blind, placebo-controlled, crossover study in 24 children with PWS at three academic institutions using 5 days of intranasal Oxytocin (IN-OT) or 5 days of intranasal placebo spray, followed by a 4 week washout period, and then patients returned for 5 days of treatment with the alternate source. Questionnaires, including the Aberrant Behavior Checklist, Social Responsiveness Scale, Repetitive Behavior Scale - Revised, and the Hyperphagia Questionnaire, as well as Clinical Global Impression scales were administered. Blood testing for sodium, potassium, and glucose levels on days 2, 4, and 6, and a 24 hr diet recall. All scales factor improvement from Day 3 to Day 6 favored Oxytocin over placebo. No single factor showed a statistically significant difference (P < 0.05) between groups at Day 6. The drug effect appeared to be diminished at Day 14. There was no evidence of a difference between Oxytocin and placebo in safety lab parameters, 60 min post dose vital signs, weight, or diet parameters. The results from this study suggest that low dose intranasal Oxytocin is safe for individuals with PWS and may result in reduction in appetite drive, and improvements in socialization, anxiety, and repetitive behaviors. Further, long-term studies with a larger population of participants are necessary to confirm these findings. The results of this study are encouraging that Oxytocin may be a safe and effective treatment for many of the issues that negatively impact individuals with PWS.

How Oxytocin Receptor (OXTR) Single Nucleotide Polymorphisms Act on Prosociality: The Mediation Role of Moral Evaluation.[Pubmed:28377734]

Front Psychol. 2017 Mar 21;8:396.

Prosociality is related to numerous positive outcomes, and mechanisms underlying individual differences in prosociality have been widely discussed. Recently, research has found converging evidence on the influence of the Oxytocin receptor (OXTR) gene on prosociality. Meanwhile, moral reasoning, a key precursor for social behavior, has also been associated with variability in OXTR gene, thus the relationship between OXTR and prosociality is assumed to be mediated by moral evaluation. The current study examines the relationship in question, and includes gender as a potential moderator. Self-reported prosociality on Prosocial Tendencies Measure and evaluation on the moral acceptability of behaviors in stories from 790 Chinese adolescents (32.4% boys) were analyzed for the influence of their OXTR single nucleotide polymorphisms (SNPs). Results showed that SNP at site rs2254298 was indirectly associated with prosocial behaviors via moral evaluation of behaviors, and this effect was moderated by gender. Our findings suggest an indirect association between genetic variations in OXTR and prosociality through moral evaluation, indicating the potential pathway from genetic variability to prosociality through level of moral development. We also provide some evidence that the role of Oxytocin system may to some extent depend on gender. These findings may promote our understanding of the genetic and biological roots of prosociality and morality.

Oxytocin and opioid addiction revisited: old drug, new applications.[Pubmed:28378414]

Br J Pharmacol. 2018 Jul;175(14):2809-2824.

Opioid addiction has devastating health and socio-economic consequences, and current pharmacotherapy is limited and often accompanied by side effects, thus novel treatment is warranted. Traditionally, the neurohypophyseal peptide Oxytocin (OT) is known for its effects on mediating reward, social affiliation and bonding, stress and learning and memory. There is now strong evidence that OT is a possible candidate for the treatment of drug addiction and depression-addiction co-morbidities. This review summarizes and critically discusses the preclinical evidence surrounding the consequences of pharmacological manipulation of the Oxytocinergic system on opioid addiction-related processes, as well as the effects of opioids on the OT system at different stages of the addiction cycle. The mechanisms underlying the effects of OT on opioid addiction, including OT' interaction with the monoaminergic, glutamatergic, opioidergic systems and its effect on the amygdala, the hypothalamic-pituitary-adrenal axis and on memory consolidation of traumatic memories, are also reviewed. We also review clinical evidence on the effects of intranasal OT administration on opioid-dependent individuals and discuss the therapeutic potential along with the limitations that accompany OT-based pharmacotherapies. Review of these studies clearly indicates that the OT system is profoundly affected by opioid use and abstinence and points towards the OT system as an important target for developing pharmacotherapies for the treatment of opioid addiction and co-existing affective disorders, thereby preventing relapse. Therefore, there is a clear need for clinical studies assessing the efficacy of OT-based pharmacotherapies in opioid addiction. LINKED ARTICLES: This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

Signal transduction pathways of the human V1-vascular, V2-renal, V3-pituitary vasopressin and oxytocin receptors.[Pubmed:10074787]

Prog Brain Res. 1998;119:147-61.

Vasopressin (VP) and Oxytocin (OT) are cyclic nonapeptides whose actions are mediated by stimulation of specific G protein-coupled receptors (GPCRs) currently classified into V1-vascular (V1R), V2-renal (V2R) and V3-pituitary (V3R) VP receptors and OT receptors (OTR). The recent cloning of the different members of the VP/OT family of receptors now allows the extensive characterization of the molecular determinants involved in ligand binding and signal transduction pathways coupled to a given VP/OT receptor subtype in stably transfected mammalian cell lines. In this article, we review the present knowledge of the signal transduction pathways coupled to the different VP/OT receptor subtypes and we present new observations derived from the study of each human VP or OT receptor subtype stably expressed in CHO cells.

Vasopressin and oxytocin receptors in the central nervous system.[Pubmed:8853957]

Crit Rev Neurobiol. 1996;10(1):119-54.

This review concentrates on the pharmacological properties and the regional distribution of the arginine vasopressin (AVP) and Oxytocin (OT) receptors that are present in the central nervous system. Of particular interest are the kinetics and the pharmacological profiles of these receptors that resemble those present at the periphery. However, their transduction mechanisms need to be further investigated. This should be rendered easier by molecular biology technology. The current knowledge of the anatomical distribution of AVP and OT receptors in the brain is reviewed. Also of great interest for double labeling studies will be the receptor antibodies, now being developed. The existence of additional receptors (AVP4-9) is examined, and aspects of the regulation of the receptors' expression in relation to the age, the species, and the hormonal status or following injury are also discussed.

Oxytocin (α-Hypophamine) is a mammalian neurohypophysial hormone; its actions are mediated by specific, high-affinity oxytocin receptors; ligand of oxytocin receptor.

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