Stress, social buffering, and oxytocin regulation

压力、社交缓冲和催产素调节

• 批准号: 9234310
• 负责人: ZUOXIN WANG
• 金额: $ 37.43万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-09 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234310
• 关键词: Agonist; Animal Model; Anxiety; Anxiety Disorders; Attenuated; Behavior; Behavioral; Bilateral; Brain; Buffers; Cannulas; Clinical Treatment; Confocal Microscopy; Corticosterone; Corticotropin-Releasing Hormone; Data; Dose; Exposure to; Female; Gene Expression; Health; Home environment; Hormonal; Human; Hypothalamic structure; Immobilization; Impairment; Implant; Individual; Injectable; Investigation; Knowledge; Mammals; Mediating; Mental Depression; Mental Health; Mental disorders; Microtus; Neurobiology; Neuropeptides; Outcome; Oxytocin; Pair Bond; Partner in relationship; Pharmacology; Physiological; Plant Roots; Play; Psyche structure; Psychological Stress; Receptor Gene; Recovery; Regulation; Reporting; Risk; Role; Sex Characteristics; Siblings; Social Behavior; Social Interaction; Social support; Stimulus; Stress; Stress and Coping; Testing; Therapeutic; Vasopressins; affiliative behavior; anxiety-like behavior; behavior test; biobehavior; biological adaptation to stress; biological systems; gamma-Aminobutyric Acid; hypothalamic-pituitary-adrenal axis; immunocytochemistry; improved; in vivo; insight; male; neurobiological mechanism; neurochemistry; neuromechanism; paraventricular nucleus; physical conditioning; prairie vole; protein expression; psychological distress; receptor; response; sex; social; social attachment; stress management

Project Summary/Abstract Psychological stress can induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing the function of multiple biological systems and posing a risk to mental and physical health. In contrast, positive social interactions, especially social support from deeply rooted social bonds, can ameliorate stress-induced mental, physiological, and behavioral deficits and improve an individual's overall well-being—a phenomenon known as social buffering [1, 2]. Such social buffering effects have been described in both human [3-5] and animal models [6, 7]. Although we have begun to understand the neuromechanisms underlying biobehavioral responses to psychological stress, little is known about the neuromechanisms by which social support buffers the stress response [1]. This is largely due to the difficulties inherent in studying neurobiological mechanisms in humans as well as a lack of appropriate animal models to assess the effects of social buffering. Recently, the socially monogamous prairie vole (Microtus ochrogaster) has emerged as an animal model to study the neurobiology of social behavior. In prairie voles, mating induces pair bonding, which is regulated by several neurochemicals including oxytocin (OT), vasopressin (AVP), corticotrophin releasing hormone (CRH), and gamma-aminobutyric acid (GABA) [8, 9]. Pair bonding reduces stress-induced anxiety-like behavior by attenuating the action of the HPA axis [10]. Interactions with the partner also promote the release of central OT [11], which plays a role in attenuating the biobehavioral response to stress in female voles [12]. Using this unique animal model, we propose, in Specific Aim 1, to examine how social buffering by a sibling cage mate or a bonding partner attenuates immobilization (IMO)-induced stress responses in male and female prairie voles. We will examine the effects of social buffering on (1) anxiety-like, depression-like, and affiliative behaviors, (2) circulating levels of corticosterone (CORT), (3) CRH, OT, AVP, GABA, and their receptors gene and protein expression in the paraventricular nucleus of the hypothalamus (PVN), and (4) neurochemical release in the PVN during IMO and social buffering. In Specific Aim 2, we will perform pharmacological manipulations with behavioral testing to examine the functional role of PVN OT, and its interactions with GABA, CRH and AVP, in the social buffering of the stress response. In Specific Aim 3, we will examine the neurochemical and physiological involvement of PVN neuromicrocircuitry in the regulation of social buffering. Data from this study will not only enhance our understanding of sex differences in the neurochemical regulation of social buffering of stress responses but also further establish a much needed animal model for such investigation.

项目总结/摘要 心理应激可引起下丘脑-垂体-肾上腺（HPA）轴激活，损害神经元的功能。 这是一个多生物系统的功能，并对身心健康构成风险。相比之下，积极 社会互动，特别是来自根深蒂固的社会纽带的社会支持，可以改善压力引起的 心理，生理和行为缺陷，并改善个人的整体福祉-一种现象 这就是所谓的社会缓冲（Social Buffering）[1，2]。这种社会缓冲效应在人类[3 - 5]和 动物模型[6，7]。虽然我们已经开始了解生物行为背后的神经机制， 社会支持对心理压力的反应，对社会支持缓冲的神经机制知之甚少 应激反应[1]。这在很大程度上是由于研究神经生物学机制的固有困难， 人类以及缺乏适当的动物模型来评估社会缓冲的影响。近日 社会一夫一妻制的草原田鼠（Microtus ochrogaster）已经成为研究 社会行为的神经生物学在草原田鼠中，交配诱导了配偶结合，这是由几个因素调节的。 神经化学物质，包括催产素（OT）、加压素（AVP）、促肾上腺皮质激素释放激素（CRH）和 γ-氨基丁酸（GABA）[8，9]。配对结合通过以下方式减少压力诱导的焦虑样行为： 减弱HPA轴的作用[10]。与合作伙伴的互动也促进了中心OT的释放 [11]，其在减弱雌性田鼠对压力的生物行为反应中起作用[12]。使用此 独特的动物模型，我们建议，在具体目标1，研究如何社会缓冲的兄弟姐妹笼交配或 结合伴侣减弱固定（IMO）引起的压力反应，在男性和女性草原田鼠。 我们将研究社会缓冲对（1）焦虑样、抑郁样和亲和行为的影响， (2)（3）CRH、OT、AVP、GABA及其受体基因， 下丘脑室旁核（PVN）蛋白表达;（4） 在IMO和社会缓冲期间的PVN。在具体目标2中，我们将进行药理学操作 用行为测试来检查PVN OT的功能作用，以及它与GABA、CRH和 AVP，在应激反应的社会缓冲中。在具体目标3中，我们将研究神经化学物质， PVN神经微回路在社会缓冲调节中的生理参与。数据从该 这项研究不仅将增强我们对社会神经化学调节的性别差异的理解， 缓冲应激反应，而且还进一步建立了用于这种研究的急需的动物模型。