Oxytocin regulation of social buffering following stress

描述(申请人提供)：应激性生活事件后的社会支持可以减弱应激反应系统，如激活下丘脑-垂体-肾上腺(HPA)轴，并降低心理困扰或恐慌症的几率；这被称为社交缓冲。当支持来自社会伙伴(例如，配偶)时，情况尤其如此。然而，涉及社会支持的生物学因素及其在应激事件后对HPA轴的影响研究不足，因为缺乏合适的动物模型来检验来自社会伴侣的支持。一夫一妻制草原田鼠(Microtus Ochrogaster)的配对结合行为被很好地描述，并代表了一个独特的模型系统来研究大脑-行为关系。这项建议将使用草原田鼠作为一个模型系统，以确定在应激经历后社会支持的神经内分泌机制，特别是神经肽催产素(OT)的中介作用。草原田鼠是一种高度社会化的一夫一妻制啮齿动物，在圈养条件下很容易繁殖，并形成对伴侣的长期社会偏好，这是结对纽带形成的传统特征。与人类一样，与社交伙伴的接触可以减弱行为和HPA轴对压力事件的反应。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)的OT释放-下丘脑室旁核(PVN)也包含促肾上腺皮质激素释放激素神经元，投射到脑下垂体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释放-减弱应激反应。因此，草原田鼠可以作为一个独特的模型系统来研究在压力事件后与社会伙伴互动的焦虑效果以及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，这一建议的结果应该是：(1)表征与社会伙伴的互动和应激事件后OT的缓解效果，(2)确定OT在生物行为应激反应的社会缓冲中所起的作用，以及(3)呈现几个脑区的神经元表型，这些脑区受到应激经历后社交互动诱导的OT释放的影响。这项研究计划代表了检验草原田鼠社会缓冲效应背后的神经生物学机制的几个步骤。

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.