Cytokine-induced Behavioral Alterations

描述(由申请人提供)： 已知，促炎细胞因子对神经内分泌和神经递质系统产生深刻影响，并诱导一系列称为疾病行为的行为改变。此外，患有炎症性疾病和接受高剂量细胞因子(如干扰素-α)治疗的传染病和癌症患者的行为变化与原发性抑郁症患者的行为变化重叠。细胞因子给药的动物模型对于阐明细胞因子作用于中枢神经系统以影响行为和精神障碍的发展的机制是必要的。这项拟议的研究将测量干扰素-α对猴子行为的急性和慢性影响，以及对细胞因子白介素1、肿瘤坏死因子-α和白介素6、激素皮质醇(CORT)和促肾上腺皮质激素(ACTH)、促肾上腺皮质激素释放因子(CRH)和单胺类神经递质水平的外周和中枢诱导。这项工作将建立行为终点，并确定未来测试药物的目标，这些药物可以预防或逆转与炎症相关的神经精神症状。

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.