Rhesus Model for Proinflammatory Influences on Depression

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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.