Neural Mechanisms underlying Social Stress

描述（由申请人提供）：社会压力有助于严重精神障碍的潜在症状的表达和增强。先前的研究表明，社会压力引起大脑边缘系统内单胺神经递质如5-羟色胺（5-HT）和多巴胺（DA）活性的显著改变。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。然而，目前还不清楚是否社会压力的感知或对这些压力源的行为反应的产生，或两者都是由边缘单胺活性介导的。此外，在边缘系统本身内，杏仁核的活动被认为可以改变多巴胺在丘脑核（NAc）中的释放。这种相互作用似乎与边缘单胺介导的社会压力有关，但其机制尚不清楚。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系统区域之间的单胺相互作用，此外还将研究社会压力感知和压力社会互动期间行为产生的单胺相关性。拟议的研究将首先在麻醉蜥蜴中使用体内计时电流法测量NAc DA对杏仁核内5 HT增加的反应（旨在模拟社会压力期间观察到的5 HT增加）的变化。随后的实验，利用类似的方法，然后确定是否抑制性神经递质GABA介导5 HT诱导的NAc DA活性的改变。杏仁核5 HT和NAc DA活动发生在一个紧张的社会互动的变化的时间性质也将进行调查。为了实现这一目标，雄性蜥蜴将被呈现具有攻击性行为的对手的视频刺激，被操纵以代表不同程度的社会威胁。在产生任何行为反应之前，将从感知到社会威胁的动物中收集大脑，并从允许产生社会反应的单独动物组中收集大脑。杏仁核和NAc随后将被显微解剖，HPLC用于确定每个区域中的单胺活性是否作为社会压力期间感知与反应产生的函数而变化。这些研究的结果预计有影响，进一步了解神经基础的适应不良行为所产生的感知社会压力或不适当的反应，在社会情况下。

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.