Oxytocin regulation of social buffering following stress

催产素对压力后社会缓冲的调节

• 批准号: 8202364
• 负责人: Adam Steven Smith
• 金额: $ 3.51万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-03 至 2013-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8202364
• 关键词: Adrenal Glands; Amygdaloid structure; Animal Model; Anti-Anxiety Agents; Anxiety; Area; Attenuated; Behavior; Behavioral; Biological Factors; Biological Models; Blood; Blood Pressure; Brain; Brain region; Breeding; Buffers; Cells; Cessation of life; Characteristics; Child; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Data; Development; Divorce; Dose; Enzyme Immunoassay; Event; FOS gene; Female; Fluorescence; Glucocorticoids; Heart Rate; Human; Hydrocortisone; Immunohistochemistry; Individual; Label; Laboratories; Left; Life; Measures; Mediating; Mental Health; Mental disorders; Microdialysis; Microinjections; Microtus; Neurobiology; Neurons; Neuropeptides; Neurosecretory Systems; Neurotransmitters; Nucleus Accumbens; Occupations; Oxytocin; Oxytocin Receptor; Pair Bond; Panic Disorder; Patients; Phenotype; Pituitary Gland; Plasma; Process; Radioimmunoassay; Recovery; Regulation; Research; Risk; Rodent; Role; Sampling; Social Behavior; Social Interaction; Social support; Source; Spouses; Stress; Stressful Event; System; Testing; Therapeutic; Woman; Work; biobehavior; biological adaptation to stress; brain behavior; cohort; experience; hypothalamic-pituitary-adrenal axis; male; paraventricular nucleus; physical conditioning; prairie vole; preference; programs; psychological distress; putamen; response; restraint stress; social; stress management; stressor

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.

描述（由申请人提供）：生活压力事件后的社会支持可以减弱压力反应系统，例如下丘脑-垂体-肾上腺（HPA）轴的激活，并减少心理困扰或恐慌症的几率；这就是所谓的社交缓冲。当来自社会伙伴（例如配偶）的支持时尤其如此。然而，由于缺乏可以检查社会伙伴支持的适当动物模型，与社会支持相关的生物因素及其在压力事件后对 HPA 轴的影响尚未得到充分研究。一夫一妻制的草原田鼠（田鼠）的配对行为得到了很好的表征，并代表了研究大脑行为关系的独特模型系统。该提案将使用草原田鼠作为模型系统来确定压力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）的调节作用。草原田鼠是一种高度社会化、一夫一妻制的啮齿动物，在圈养条件下很容易繁殖，并对伴侣形成长期的社会偏好，这是配对关系形成的传统特征。与人类一样，与社交伙伴的接触可以减弱行为轴和 HPA 轴对压力事件的反应。此外，积极的社交互动会促进草原田鼠大脑 OT 的释放，而下丘脑室旁核 (PVN) 中的 OT 释放也会减弱应激反应性。PVN 还含有促肾上腺皮质激素释放激素神经元，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。因此，草原田鼠可以作为一个独特的模型系统来研究压力事件后与社会伙伴互动的抗焦虑作用以及 OT 的潜在中介作用。通过在社会缓冲压力范式中使用草原田鼠，该提案的结果应该：（1）表征压力事件后与社会伙伴和 OT 互动的抗焦虑作用，（2）确定 OT 在生物行为压力反应的社会缓冲中的作用，以及（3）在压力经历后受社交互动诱导的 OT 释放影响的几个大脑区域中呈现神经元表型。该研究计划代表了研究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。 公共卫生相关性：压力生活事件后的社会支持可以减弱压力反应，但不幸的是，压力引起的精神和身体健康障碍风险最大的个人也可能缺乏适当水平和来源的社会支持。在这里，考虑到压力对个人健康的巨大影响，我建议使用社会一夫一妻制的草原田鼠（Microtus ochrogaster）作为模型系统来研究在压力生活事件后调节社会支持的神经内分泌机制。更好地了解神经内分泌机制可能会指导临床医生针对有经历压力生活事件和随后与压力相关的心理障碍风险的患者，特别是那些社会支持不足的患者，采取潜在的治疗方法——针对中枢神经递质系统开发抗焦虑药。