Neural Mechanisms underlying Social Stress

描述(由申请人提供)：社会压力导致严重精神障碍潜在症状的表达和强化。先前的研究表明，社交压力会引起大脑边缘系统内单胺类神经递质的显著变化，如5-羟色胺(5-羟色胺)和多巴胺(DA)。单胺活动的变化似乎也是精神障碍病理的一个主要组成部分。然而，尚不清楚对社会压力的感知或对这些应激源的行为反应的产生，或者两者兼而有之，是由边缘单胺活动介导的。此外，在边缘系统本身，已知杏仁核活动会改变伏隔核(NAC)中DA的释放。这种相互作用似乎与边缘单胺调节社会压力有关，但其机制尚不清楚。该项目将使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，此外还将研究在应激社会互动中社会压力感知和行为产生的单胺能关联。这项拟议的研究将首先使用麻醉蜥蜴的活体计时电流测量法，测量杏仁核内5HT含量增加时NAC DA的变化(旨在模拟社会应激期间看到的5HT含量增加)。随后使用类似方法的实验将确定抑制性神经递质GABA是否介导了5HT诱导的NAC DA活性的改变。在紧张的社会互动中，杏仁核5-羟色胺和NAc-DA活动的变化的时间性质也将被调查。为了实现这一点，雄性蜥蜴将被呈现给咄咄逼人的对手的视频刺激，这些视频被操纵以代表不同程度的社会威胁。大脑将在感知到社会威胁后，在产生任何行为反应之前从动物身上收集，并从允许产生社会反应的另一组动物那里收集。随后将对杏仁核和NAC进行显微解剖，用高效液相色谱法来确定在社会应激过程中，每个区域的单胺活动是否随着感知和反应产生的变化而变化。这些研究的发现有望对进一步理解不良适应行为的神经基础有所启示，这些不良行为是由对社会压力的感知或在社会情境中的不当反应引起的。

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.