Ethanol Withdrawal and Cytokines

描述（由申请人提供）：急性酒精暴露的戒断会产生深刻的行为变化，包括探索和运动活动减少以及社会互动受到抑制。这些行为变化是“宿醉”状态的特征，与传染性病原体或注射促炎细胞因子引起的急性疾病期间通常观察到的疾病行为非常相似。因此，我们提出，大鼠急性酒精暴露戒断期间的行为反应可能被视为类似疾病的行为反应，这种行为反应是由传统上与免疫激活相关的炎症相关途径的激活引发和维持的。我们的初步数据表明，在中枢神经系统中，白细胞介素-1的转录活性显著增加，这对免疫反应的正常进展和疾病行为的产生至关重要。因此，以下建议的目标是（目标1）建立宿醉产生的细胞因子反应的时空特征，（目标2）确定宿醉产生的细胞因子反应的可能细胞和神经化学机制，以及（目标3）在大鼠宿醉期间观察到的中枢细胞因子增加与疾病样行为变化之间建立积极的机制联系。

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.