Behavioral autonomic and endocrine regulation in depression and heart disease

描述（由申请人提供）：本研究将运用行为学、自主神经学和神经内分泌学的方法来研究涉及催产素的神经机制在抑郁症和心脏病之间存在关联的假设。与消极影响有关的疾病，如抑郁和焦虑，是公认的心血管疾病风险因素；这种关系对于具有特定脆弱性的个人（例如有心脏病家族史的人或人口老龄化的人）尤其重要。对压力源的心理和生理反应，特别是在社会环境中的反应，在情感症状和行为的发展中起着重要作用，并与心血管功能障碍直接相关。此外，有证据表明，催产素介导与压力和社会经验相关的行为和生理过程，因此这种神经肽可能在情绪和心血管疾病之间的联系中具有机制作用。目前的研究项目将使用啮齿动物模型，社会一夫一妻制草原田鼠，来研究对社会压力源（社会孤立）的行为、神经内分泌和自主反应，以及这些反应背后潜在的催产素机制。越来越多的证据表明，草原田鼠为研究对社会经验的反应性提供了一个独特的模型系统，并且该物种在研究与情绪和心脏功能相关的自主机制方面具有实用价值。实验1将采用(a)与抑郁相关的行为测试，(b)自主神经和心脏参数的连续记录，以及(c)循环和中枢神经系统激素和肽的测量，以检验社会隔离诱导与抑郁和心血管疾病相关的行为和生理反应的假设（具体目标1）。实验2将采用(a)长期给药催产素和(b)给药催产素拮抗剂，以检验催产素能机制是对社会孤立的行为、自主神经和神经内分泌反应的具体基础这一假设（具体目标2）。本研究提出了社会环境影响行为、生理和脑功能的新机制，可以促进抑郁症和心血管疾病患者更综合治疗的发展。行为、脑功能和心血管系统之间存在着重要的相互作用；这些相互作用的一个例子是抑郁症和心脏病之间的联系。目前的研究项目将通过在动物模型中研究行为、内分泌（激素）、自主神经（心血管功能的控制）和参与调节情绪和心血管功能的大脑过程来直接调查这些疾病之间的联系。这项研究可以为抑郁症和心脏病患者提供更有效的治疗方法。

DESCRIPTION (provided by applicant): This research will use behavioral, autonomic, and neuroendocrine approaches to investigate the hypothesis that neural mechanisms involving oxytocin underlie the documented association between depression and heart disease. Disorders relating to negative affect, such as depression and anxiety, are recognized risk factors for cardiovascular disease; this relationship is especially important for individuals with specific vulnerabilities (such as persons with a family history of heart disease or aging populations). Psychological and physiological responses to stressors, and in particular reactions in the social context, play an important role in the development of affective symptoms and behaviors, and have been linked directly to cardiovascular dysfunction. Furthermore, evidence indicates that oxytocin mediates behavioral and physiological processes associated with stress and social experiences, and therefore this neuropeptide may have a mechanistic role in the link between mood and cardiovascular disorders. The current research project will use a rodent model, the socially monogamous prairie vole, to study the behavioral, neuroendocrine, and autonomic responses to a social stressor (social isolation), and the potential oxytocinergic mechanisms that underlie these responses. Converging evidence suggests that the prairie vole provides a unique model system for studying responsiveness to social experiences, and that this species has utility for studying autonomic mechanisms related to mood and cardiac function. Experiment 1 will employ (a) behavioral tests relevant to depression, (b) continuous recording of autonomic and cardiac parameters, and (c) measures of circulating and central nervous system hormones and peptides, to test the hypothesis that social isolation induces behavioral and physiological responses relevant to depression and cardiovascular disease (Specific Aim 1). Experiment 2 will employ (a) chronic administration of oxytocin and (b) administration of an oxytocin antagonist, to test the hypothesis that oxytocinergic mechanisms underlie specifically the behavioral, autonomic, and neuroendocrine responses to social isolation (Specific Aim 2). This research proposes a novel mechanism by which the social environment impacts behavior, physiology, and brain function, which can promote the development of more comprehensive treatments for patients with depression and cardiovascular disease. There are important interactions among behavior, brain function, and the cardiovascular system; one such example of these interactions is the association between depression and heart disease. The current research project will investigate directly the link between these conditions by studying in an animal model the behavioral, endocrine (hormones), autonomic (control of cardiovascular function), and brain processes involved in mediating mood and cardiovascular function. This research can lead to the development of more effective treatments for patients with depression and heart disease.