Rhesus Model for Proinflammatory Influences on Depression

描述（由申请人提供）：社会关系的破坏是抑郁症发展的主要风险因素。这种影响的机制，以及为什么个体对这种影响的脆弱性差异很大，是目前许多研究的重点，但仍然知之甚少。建立一个简单、实用的非人灵长类动物模型将极大地促进这一努力。在加州国家灵长类动物研究中心的初步观察表明，雄性恒河猴在从大型户外社会群体转移到个人室内住宅后不久经常表现出抑郁样的行为反应，这种易感性以可预测的方式在个体之间变化，而且这种反应发生的频率在过去被低估或忽视，因为雄性恒河猴倾向于成为在人类观察者面前注意或警觉。其他观察结果表明，全身促炎活性的增加有助于这种抑郁的结果。因此，两个具体的目标将探讨适合单独安置雄性恒河猴作为一个实用的模型，研究社会压力和抑郁症之间的联系，以及可能的作用，促炎因子在介导这种效果。第一个目标将系统地研究频率与性成熟的雄性恒河猴显示抑郁样的行为反应时，从社会群体中删除，并放置在个人室内住房，协会的行为反应与促炎活动的措施，以及这些影响的关系稳定的生物行为特征的男性。第二个目标是研究环氧合酶抑制剂降低个体住房抑郁样反应的能力。这一目标将提供一个直接的测试的促炎机制，建议介导抑郁样行为反应。该实验还将提供一个初步的测试， 简单的预防措施，以抵消猴子模型中社会隔离的影响。

DESCRIPTION (provided by applicant): The disruption of social relationships is a major risk factor for the development of depressive illness. The mechanisms underlying this effect, as well as why individuals vary widely in vulnerability to this influence, are the focus of much current research, but are still poorly understood. The establishment of a simple, practical, non-human primate model would greatly facilitate this effort. Preliminary observations at the California National Primate Research Center indicate that male rhesus macaques often display a depressive-like behavioral response soon after being moved from large outdoor social groups to individual indoor housing, that susceptibility varies among individuals in a predictable fashion, and that the frequency with which this reaction occurs has been underestimated or overlooked in the past due to the tendency of male rhesus to become attentive or alert in the presence of a human observer. Other observations suggest that an increase in systemic proinflammatory activity contributes to this depressive outcome. Therefore, two specific aims will explore the suitability of rehousing males rhesus monkeys individually as a practical model for studying the link between social stress and depression, as well as the possible role of proinflammatory factors in mediating this effect. The first aim will systematically examine the frequency with which sexually mature male rhesus macaques display a depressive-like behavioral reaction when removed from a social group and placed in individual indoor housing, the association of the behavioral reaction with measures of proinflammatory activity, and the relation of these effects to stable biobehavioral characteristics of the males. The second aim will examine the ability of a cyclooxygenase inhibitor to reduce the depressive-like response to individual housing. This aim will provide a direct test of a proinflammatory mechanism suggested to mediate depressive-like behavioral reactions. The experiment will also provide an initial test of a simple prophylactic measure to counter effects of social isolation in a monkey model.