Stress, social buffering, and oxytocin regulation

压力、社交缓冲和催产素调节

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要心理压力会诱发下丘脑-垂体-肾上腺（HPA）轴的激活，损害相比之下，对多种生物系统的功能和对精神和身体健康构成风险。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精神、生理和行为缺陷并改善个人的整体健康——一种现象称为社交缓冲 [1, 2]，这种社交缓冲效应已在人类 [3-5] 和尽管我们已经开始了解生物行为背后的神经机制[6, 7]。对于心理压力的反应，人们对社会支持缓冲的神经机制知之甚少应激反应[1]主要是由于研究神经生物学机制固有的困难。人类以及缺乏适当的动物模型来评估社会缓冲的影响。社会一夫一妻制的草原田鼠（Microtus ochrogaster）已成为研究在草原田鼠的社会行为神经生物学中，交配会诱导配对关系，这是由多种因素调节的。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] 通过减少压力诱发的焦虑样行为。减弱 HPA 轴的作用 [10] 与伴侣的相互作用也促进中枢 OT 的释放。 [11]，它在减弱雌性田鼠对压力的生物行为反应方面发挥作用[12]。独特的动物模型，我们建议，在具体目标 1 中，研究兄弟姐妹笼中伴侣或亲密伴侣可以减轻雄性和雌性草原田鼠因固定（IMO）引起的应激反应。我们将研究社交缓冲对（1）类焦虑、类抑郁和亲和行为的影响， (2) 皮质酮 (CORT) 的循环水平，(3) CRH、OT、AVP、GABA 及其受体基因和下丘脑室旁核 (PVN) 中的蛋白质表达，以及 (4) 神经化学物质的释放 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。通过行为测试来检查 PVN OT 的功能作用及其与 GABA、CRH 和 AVP，在压力反应的社会缓冲中，我们将检查神经化学和压力反应。 PVN 神经微电路在社交缓冲调节中的生理参与来自此的数据。研究不仅将增强我们对社会神经化学调节中性别差异的理解缓冲应激反应，还进一步建立此类研究急需的动物模型。