The protective effect of oxytocin on social isolation: physiological mechanisms

催产素对社会隔离的保护作用：生理机制

• 批准号: 8141629
• 负责人: Jason R Yee
• 金额: $ 5.13万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141629
• 关键词: Abbreviations; Address; Adrenal Glands; Age; Aging; Amygdaloid structure; Analysis of Variance; Animal Housing; Animal Model; Animals; Anxiety; Argipressin; Autonomic nervous system; Behavioral; Bereavement; Brain; Buffers; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Data; Disease; Dose; Elderly; Electrocardiogram; Emotional; Enzyme-Linked Immunosorbent Assay; FOS gene; Feedback; Goals; Grief reaction; Health; Hormones; Human; Hypothalamic structure; Individual; Lead; Life; Measures; Mediating; Mental Health; Methods; Microtus; Modeling; Morbidity - disease rate; Neuropeptides; Neurosecretory Systems; Nucleus solitarius; Outcome; Outcome Study; Oxytocin; Oxytocin Receptor; Peptides; Peripheral; Physiological; Pituitary Gland; Play; Prevention; Psyche structure; Research; Risk Factors; Rodent; Role; Social isolation; Social support; Stress; Supplementation; Swimming; System; Testing; Vagus nerve structure; Work; age related; base; behavior test; dorsal motor nucleus; intraperitoneal; mortality; paraventricular nucleus; physical conditioning; prairie vole; prevent; protective effect; release factor; research study; social; social attachment; social separation; stressor; subcutaneous; supraoptic nucleus; therapeutic target; translational study

DESCRIPTION (provided by applicant): Social relationships have a significant effect on overall health, and the bereavement and grief associated with losing a close relationship is associated with increased rates of morbidity and mortality. The general j goal of this application is to begin deconstructing the mechanisms through which social relationships are beneficial to mental and physical health, especially in aging. The hypothesis to be examined suggests that oxytocin (OT) plays a central role in buffering against emotional and autonomic reactivity, including stress and anxiety which may have broad consequences for health in old age. To dissect the physiological j mechanisms that underie the connection between stress and sociality, we will use the prairie vole (Microtus j ochrogaster), an animal similar to humans (but unique among rodents) in its tendency to form selective, long-lasting social bonds. Prairie voles also have a human-like autonomic nervous system and produce high levels of OT, making them an ideal model for translational studies on the mechanisms underlying the connection between social relationships and health. The proposed integrative experiments will examine behavioral, neuroendocrine and autonomic changes: following social separation and isolation, as a function of the presence or absence of OT. Research has shown that OT promotes social affiliation and buffers against stressors. However, recent work has also shown that OT is heightened after a long period of separation from a familiar social partner. The experiments proposed herein will closely examine the function of this separation-induced rise in OT by administering exogenous OT, or by blocking the actions of endogenous OT with a selective antagonist. Comparisons between central and peripheral administrations will demonstrate where OT is acting to produce changes in the emotional and physiological reactivity to stressors. Clarifying the mechanisms through which- social separation and isolation lead to detrimental changes will ultimately result in more targeted therapeutic approaches that hold promise for both prevention and treatment of age-related disease. 1: The loss of close social relationships, especially in old age, is potentially one of the strongest risk factors for mental and physical decline, but its mechanisms remain largely unknown. This work seeks to understand: the underlying physiological mechanisms in order to guide both behavioral and pharmacological efforts to prevent disease and promote health in the elderly.

描述（由申请人提供）：社会关系对整体健康有重大影响，与失去亲密关系有关的丧亲和悲伤与发病率和死亡率的提高有关。该应用的总体J目标是开始解构社会关系对身心健康有益的机制，尤其是在衰老中。要研究的假设表明，催产素（OT）在缓冲情绪和自主反应性方面起着核心作用，包括压力和焦虑，这可能会对老年人的健康产生广泛的影响。为了剖析压力与社会性之间联系的生理J机制，我们将使用草原Vole（Microtus j ochrogaster），这是一种类似于人类（但在啮齿动物之间）的动物，以形成选择性，持久的社会纽带。草原田鼠还具有类似人类的自主神经系统，并产生了高水平的OT，使其成为转化社会关系与健康之间联系的机制的理想模型。提出的综合实验将检查行为，神经内分泌和自主神经的变化：在社会分离和隔离之后，作为OT存在或不存在的函数。研究表明，OT可以促进社会隶属关系和缓冲压力源。但是，最近的工作还表明，在与熟悉的社会伙伴分离长期之后，OT会加剧。本文提出的实验将通过施用外源OT或通过选择性拮抗剂阻止内源性OT的作用来仔细检查这种分离引起的OT的升高。中央和外围管理之间的比较将证明OT在何处表现出对压力源的情绪和生理反应性的变化。阐明通过社会分离和隔离导致有害变化的机制最终会导致更具针对性的治疗方法，从而有望预防和治疗与年龄相关的疾病。 1：失去紧密的社会关系，尤其是在老年时，可能是精神和身体衰落的最强大风险因素之一，但其机制仍然很大。这项工作试图理解：基本的生理机制，以指导行为和药理努力，以预防疾病和促进老年人的健康。

项目成果

Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei.

• DOI: 10.1016/j.yhbeh.2016.01.010
• 发表时间: 2016-04
• 期刊: Hormones and behavior
• 影响因子: 3.5
• 作者: Yee JR;Kenkel WM;Frijling JL;Dodhia S;Onishi KG;Tovar S;Saber MJ;Lewis GF;Liu W;Porges SW;Carter CS
• 通讯作者: Carter CS