Ethanol Withdrawal and Cytokines

描述（由申请人提供）：从急性酒精暴露中戒断会导致行为发生深刻变化，包括探索和运动活动减少以及社会互动受到抑制。这些行为变化表征了“宿醉”状态，并且与通常在由感染因子或注射促炎性细胞因子产生的急性疾病期间观察到的疾病行为非常相似。因此，我们提出，在急性酒精暴露大鼠戒断过程中的行为反应可以被视为疾病样行为反应，启动和维持传统上与免疫激活相关的炎症相关途径的激活。我们的初步数据表明，在中枢神经系统的网站，是至关重要的免疫反应的正常进展和疾病行为的产生的白细胞介素-1的转录活性的强劲增长。因此，以下建议的目的是（目的1）建立由宿醉产生的细胞因子应答的时间和空间特征，（目的2）鉴定由宿醉产生的细胞因子应答的可能的细胞和神经化学机制，以及（目的3）在大鼠中在宿醉期间观察到的中枢细胞因子增加和疾病样行为变化之间建立正机制联系。

DESCRIPTION (provided by applicant): Withdrawal from acute alcohol exposure produces profound changes in behavior including reduced exploration and locomotor activity as well as suppressed social interaction. These behavioral changes characterize the "hangover" state and are remarkably similar to sickness behaviors that are typically observed during acute illness produced by infectious agents or injection of pro-inflammatory cytokines. We therefore propose that behavioral responses during withdrawal from acute alcohol exposure in rats may be viewed as sickness-like behavioral responses that are initiated and maintained by activation of inflammatory-related pathways traditionally associated with immune activation. Our preliminary data indicate robust increases in transcriptional activity of interleukin-1 in CNS sites that are crucial for normal progression of the immune response and the generation of sickness behaviors. The goal of the following proposal, therefore, is to (Aim 1) establish the temporal and spatial characteristics of cytokine responses produced by hangover, (Aim 2) to identify probable cellular and neurochemical mechanisms of cytokine responses produced by hangover, and (Aim 3) to forge a positive mechanistic link between increased central cytokines and the sickness-like behavioral changes observed during hangover in rats.