Cytokine-induced Behavioral Alterations

描述（由申请人提供）： 众所周知，促炎细胞因子对神经内分泌和神经递质系统产生深远的影响，并诱导一系列被称为疾病行为的行为变化。此外，患有炎症性疾病的患者和接受高剂量细胞因子（如干扰素（IFN）-α）治疗感染性疾病和癌症的患者会经历与原发性重度抑郁症重叠的行为变化。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疾病发展的机制是必要的。拟议的研究将测量IFN-α对猴子行为的急性和慢性影响以及对细胞因子白细胞介素（IL）-1，肿瘤坏死因子（TNF）-α和IL-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）和单胺神经递质水平的外周和中枢诱导的影响。这项工作将建立行为终点，并确定预防或逆转与炎症相关的神经精神症状的药理学药物未来测试的目标。

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.