Behavioral Despair and Interleukin-1

State University New York Binghamton, Binghamton NY

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Abstract

In recent years, there has been increasing recognition that pro- inflammatory cytokines play a role in the behavioral and physiological alterations produced by exposure to psychological stressors. The data to support this conclusion comes from the findings that (a) acute stress can induce pro-inflammatory cytokine production both centrally and peripherally, (b) administration of pro-inflammatory cytokines produces many of the same behavioral and physiological consequences as acute stress exposure, and (c) blockade of pro-inflammatory cytokine activity inhibits or attenuates some behavioral and physiological consequences of acute stressor exposure. These data have led to the suggestion that production of cytokines in response to stress may provide novel insight into the etiology of stress-related disorders. Perhaps one of the most widely used animal models of stress is the forced swim test. During this stressor, rats are forced to swim in a cylinder of water from which there is no escape. After an initial period of behavioral activation characterized by repeated attempts to escape, rats then adopt a characteristic posture of immobility that has been conceptualized as behavioral despair. Given recent notions that cytokines mediate some stress-related behaviors, we explored whether the pro-inflammatory cytokine Interleukin01 (IL-1) would be elevated in rats that have been forced to swim. Our preliminary results demonstrate a robust increase in IL-1 in all peripheral tissues examined (blood, pituitary, and spleen) immediately after the forced swim session. These data raise the possibility that the immobility response observed during the forced swim stressor may be mediated by IL-1. Thus, the goal of this proposal is to characterize the time-course of the swim stress induced increase in IL-1 and determine whether the increase in IL-1 is functionally related to the changes in behavior observed during forced swim exposure.