Cytokine-induced Behavioral Alterations

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DESCRIPTION (provided by applicant): It is known that proinflammatory cytokines exert profound effects on neuroendocrine and neurotransmitter systems and induce a constellation of behavioral changes referred to as sickness behavior. Furthermore, patients with inflammatory illnesses and those treated with high doses of cytokines, such as interferon (IFN)-alpha, for infectious diseases and cancers experience behavioral changes that overlap with those of primary major depression. Animal models of cytokine administration are necessary to elucidate the mechanisms by which cytokines act on the central nervous system to affect behavior and the development of psychiatric disorders. The proposed study will measure the acute and chronic effects of IFN-alpha on behavior and on the peripheral and central induction of the cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6, the hormones cortisol (CORT) and adrenocorticotropic hormone (ACTH), corticotropin releasing factor (CRH) and monoamine neurotransmitter levels in monkeys. This work will establish behavioral endpoints and identify targets for the future testing of pharmacological agents that prevent or reverse neuropsychiatric symptoms associated with inflammation.