Oxytocin regulation of social buffering following stress

描述（由申请人提供）：压力生活事件后的社会支持可以减弱压力反应系统，如下丘脑-垂体-肾上腺（HPA）轴的激活，并减少心理困扰或惊恐障碍的几率；这就是所谓的社会缓冲。当支持来自社会伙伴（如配偶）时尤其如此。然而，由于缺乏适当的动物模型来检验来自社会伙伴的支持，涉及社会支持的生物学因素及其对压力事件后下丘脑轴的影响尚未得到充分研究。一夫一妻制草原田鼠（Microtus ochrogaster）的配对结合行为被很好地表征，为研究脑行为关系提供了一个独特的模型系统。本研究将以草原田鼠为研究对象，研究应激后社会支持的神经内分泌机制，特别是神经肽催产素（OT）的调节作用。草原田鼠是一种高度社会化的、一夫一妻制的啮齿动物，在圈养环境中很容易繁殖，并对伴侣形成长期的社会偏好，这是伴侣关系形成的传统特征。与人类一样，与社会伙伴的接触可以减弱对压力事件的行为和HPA轴反应。此外，积极的社会互动促进草原田鼠大脑OT的释放，而下丘脑室旁核（PVN）中的OT释放（PVN还含有促肾上腺皮质激素释放激素神经元，该神经元投射到垂体以控制促肾上腺皮质激素的分泌和随后的肾上腺糖皮质激素的释放）可减弱应激反应性。因此，草原田鼠可以作为一个独特的模型系统来研究应激事件后与社会伙伴互动的焦虑效应以及OT的潜在中介作用。通过在社会缓冲应激范式中使用草原田鼠，本建议的结果应该：(1)表征应激事件后与社会伴侣和OT互动的焦虑效应，(2)确定OT在生物行为应激反应的社会缓冲中的作用，以及(3)在应激经历后受社会互动诱导的OT释放影响的几个大脑区域中存在神经元表型。本研究计划代表了在草原田鼠的社会缓冲效应的神经生物学机制检查的几个步骤。

DESCRIPTION (provided by applicant): Social support following a stressful life event can attenuate stress response systems, such as the activation of the hypothalamic-pituitary-adrenal (HPA) axis, and reduce the odds of psychological distress or a panic disorder; this is known as social buffering. This is particularly true when support is derived from a social partner (e.g., spouse). However, biological factors that are involved with social support and their influence on the HPA axis following a stressful event are understudied due to the lack of appropriate animal models that can examine support from a social partner. The pair-bonding behavior in monogamous prairie voles (Microtus ochrogaster) is well characterized and represents a unique model system to study brain-behavior relationships. This proposal will use prairie voles as a model system to identify neuroendocrine mechanisms of social support following a stressful experience, particularly the mediating effects of the neuropeptide oxytocin (OT). The prairie vole is a highly social, monogamous rodent that breeds readily in captivity and forms a long-term social preference for their partner, a traditional characteristic of pair-bond formation. Like humans, contact with a social partner can attenuate the behavioral and HPA axis response to a stressful event. In addition, positive social interactions promote brain OT release in prairie voles, and OT release in the hypothalamic paraventricular nucleus (PVN) - which also contains corticotropin-releasing hormone neurons that project to the pituitary to control adrenocorticotropic hormone secretion and subsequent adrenal glucocorticoid release - attenuates stress reactivity. Therefore, prairie voles may serve as a unique model system to study the anxiolytic effects of interaction with a social partner following a stressful event and the potentially mediating role of OT. By using prairie voles in a social buffering stress paradigm, the results from this proposal should: (1) characterize the anxiolytic effects of interactions with a social partner and OT following a stressful event, (2) identify the role that OT has in the social buffering of the biobehavioral stress response, and (3) present neuronal phenotypes in several brain regions that are influenced by social interaction-induced OT release following a stressful experience. This research program represents several steps in examining the neurobiology mechanism underlying the social buffering effect in prairie voles. PUBLIC HEALTH RELEVANCE: Social support following a stressful life event can attenuate stress responses, but unfortunately, individuals at the greatest risk for stress-induced mental and physical health disturbances may also lack the appropriate level and source of social support. Here, I propose to use the socially monogamous prairie vole (Microtus ochrogaster) as a model system to investigate the neuroendocrine mechanisms mediating social support following a stressful life event, given the immense impact stress can have on an individual's well being. A better understanding of the neuroendocrine mechanisms may direct clinicians to potential therapeutic treatments - targeting the central neurotransmitter system in the development of anxiolytics - for patients at risk of experiencing stressful life events and subsequent stress-related psychological disorders, particularly those with inadequate social support.