Rhesus Model for Proinflammatory Influences on Depression

社会关系的中断是患抑郁症的一个主要风险因素 生病了。这种效应背后的机制，以及为什么个体在 易受这种影响，是当前许多研究的重点，但仍然很少 明白了。建立一个简单、实用的非人类灵长类动物模型将极大地 促进这一努力。加州国家灵长类动物研究中心的初步观测 表明雄性恒河猴通常很快就会表现出类似抑郁的行为反应 从大型户外社会团体搬到个人室内住房后， 易感性在不同的人中以一种可预测的方式变化，而且频率随着 这种反应的发生在过去被低估或忽视了，因为 雄性恒河猴在人类观察者面前变得注意力集中或警觉的倾向。 其他观察表明，全身性促炎活性的增加有助于 这种令人沮丧的结果。因此，有两个具体目标将探讨安置的适宜性 雄性恒河猴个体作为研究社会联系的实用模型 应激和抑郁，以及促炎因子在其中的可能作用 效果。第一个目标将系统地检验性成熟男性 猕猴在离开社交场所时会表现出抑郁样的行为反应 群体和放置在单独的室内住房中，行为反应与 促炎活性的测量，以及这些影响与稳定的生物行为的关系 雄性的特征。第二个目标是检测环氧合酶的能力。 抑制剂，以减少抑郁样反应的个人住房。这一目标将提供一个 直接测试一种可能调节抑郁样行为的促炎机制 反应。这项实验还将对一种简单的预防措施进行初步测试 在猴子模型中，社会孤立的反作用。

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.