Stress, social buffering, and oxytocin regulation

项目摘要/摘要 心理应激可诱导下丘脑-垂体-肾上腺(HPA)轴的激活，损害 多个生物系统的功能，并对身心健康构成风险。相比之下，积极的 社会互动，特别是来自根深蒂固的社会纽带的社会支持，可以改善由压力引起的 精神、生理和行为缺陷并改善个人的整体幸福感--这是一种现象 这被称为社交缓冲[1，2]。这种社会缓冲效应在人类[3-5]和 动物模型[6，7]。尽管我们已经开始了解生物行为背后的神经机制 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]。这在很大程度上是由于在研究神经生物学机制方面固有的困难。 人类以及缺乏适当的动物模型来评估社会缓冲的影响。最近， 社会一夫一妻制草原田鼠(Microtus Ochrogaster)已成为研究 社会行为的神经生物学。在草原田鼠中，交配诱导配对结合，这受几个因素的调节 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应激诱导的焦虑样行为 减弱HPA轴的作用[10]。与合作伙伴的互动也促进了中央OT的释放 [11]，它在减弱雌性田鼠对应激的生物行为反应方面发挥了作用[12]。使用这个 独特的动物模型，我们建议，在特定的目标1，检查如何通过兄弟姐妹笼子配偶或 结合伙伴减弱固定(IMO)诱导的应激反应在雄性和雌性草原田鼠。 我们将考察社交缓冲对(1)类焦虑、类抑郁和从属行为的影响， (2)循环皮质酮(CORT)、(3)CRH、OT、AVP、GABA及其受体基因和 下丘脑室旁核(PVN)的蛋白表达；(4)大鼠神经化学释放 在IMO和社会缓冲期间的PVN。在特定目标2中，我们将执行药物操作 通过行为学测试来研究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。在特定的目标3中，我们将检查神经化学和 下丘脑室旁核神经微回路在调节社会缓冲中的生理作用。来自于此的数据 研究不仅会提高我们对性别差异在社会神经化学调节中的认识 缓冲应激反应，也进一步建立了此类研究亟需的动物模型。

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.