Neural Mechanisms underlying Social Stress

社会压力背后的神经机制

• 批准号: 6664769
• 负责人: MICHAEL JAMES WATT
• 金额: $ 7.03万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6664769
• 关键词: GABA receptor; amines; amygdala; behavior test; behavioral /social science research tag; computer program /software; digital imaging; dopamine; electrostimulus; ethology; high performance liquid chromatography; lizards; neuroregulation; nucleus accumbens; psychological stressor; serotonin; social competition; social perception; social psychology; stereotaxic techniques; video recording system

DESCRIPTION (provided by applicant): Social stress contributes to the expression and potentiation of symptoms underlying severe psychiatric disorders. Previous research suggests that social stress evokes significant alterations in the activity of monoamine neurotransmitters such as serotonin (5HT) and dopamine (DA) within the limbic system of the brain. Changes monoamine activity also appear to be a major component of psychiatric disorder pathology. However, it is unclear whether the perception of social stress or the production of the behavioral response to these stressors, or both, are being mediated by limbic monoamine activity. Also, within the limbic system itself, amygdalar activity is known to alter DA release in the nucleus accumbens (NAc). This interaction appears to have relevance for limbic monoamine mediation of social stress, but the mechanisms are not well understood. This project will employ a reptile model of social stress to explore monoamine interactions between these two limbic areas, in addition to investigating the monoaminergic correlates of both perception of social stress and the production of behaviors during stressful social interactions. The proposed studies will first measure changes in NAc DA in response to increased 5HT within the amygdala (designed to mimic 5HT increases seen during social stress), using in vivo chronoamperometry in anesthetized lizards. Subsequent experiments utilizing similar methodology will then determine whether the inhibitory neurotransmitter GABA mediates 5HT-induced alteration of NAc DA activity. The temporal nature of changes in amygdala 5HT and NAc DA activity occurring during a stressful social interaction will also be investigated. To achieve this, male lizards will be presented with video stimuli of aggressively behaving opponents, manipulated to represent varying levels of social threat. Brains will be collected from animals upon perception of the social threat before production of any behavioral response, and from a separate group of animals allowed to produce social responses. The amygdala and NAc will be subsequently microdissected, with HPLC used to determine whether monoamine activity in each region changes as a function of perception versus response production during social stress. Findings from these studies are anticipated to have implications for further understanding the neural bases of maladaptive behaviors arising from either the perception of social stress or inappropriate responding in social situations.

描述（由申请人提供）：社会压力有助于表达和增强严重精神疾病的症状。先前的研究表明，社会压力引起了单胺神经递质（例如5-羟色胺（5HT）和多巴胺（DA））活性的重大变化。单胺活性的变化似乎也是精神疾病病理学的主要组成部分。但是，尚不清楚社会压力的感知还是对这些压力源的行为反应的产生，或两者兼有边缘单胺活性介导。同样，在边缘系统本身中，已知杏仁核活性会改变伏隔核（NAC）中的DA释放。这种相互作用似乎与边缘单胺的社会压力介导相关，但是这些机制尚未得到充分理解。该项目将采用社会压力的爬行动物模型来探索这两个边缘区域之间的单胺相互作用，此外还要研究在压力社交互动期间对社会压力的看法和行为产生的单胺能相关性。拟议的研究将首先衡量NAC DA的变化，以响应杏仁核内的5HT增加（旨在模仿在社会压力期间看到的5HT增加），并使用麻醉的蜥蜴中的体内计时度计。然后，利用类似方法的随后实验将确定抑制性神经递质GABA是否介导5HT诱导的NAC DA活性改变。还将研究在紧张的社交互动期间发生杏仁核5HT和NAC DA活动的变化的时间性质。为了实现这一目标，男性蜥蜴将以积极行事的对手的视频刺激呈现，被操纵以代表不同水平的社会威胁。在产生任何行为反应之前，将从动物感知社会威胁时从动物中收集大脑，并从允许产生社会反应的单独动物群体中收集大脑。随后将对杏仁核和NAC进行显微解剖，HPLC用于确定每个区域中的单胺活性是否会随着社会压力期间的感知和反应产生的函数而变化。预计这些研究的结果将对进一步理解因对社会压力的看法或在社会情况下的反应不当而导致不良适应行为的神经基础具有影响。