The Role of Serotonin in Alcohol-Withdrawal Induced Anxiety

摘要 酗酒是一个巨大的公共卫生问题。虽然我们的知识有了很大的进步， 对于这种疾病，我们缺乏有关导致这种疾病的生物学机制的基本知识。 酒精滥用的慢性复发性病理。据推测，酒精暴露会改变功能 在大脑中对情绪调节至关重要的区域，这些变化是持续改变的基础， 行为5-羟色胺（5-HT）系统与一系列精神疾病的病理生理学有关。 条件，最显着的焦虑症和抑郁症（两个条件共病与酒精使用 疾病）。改变的5 HT信号传导已被认为有助于渴望和复发，以及 增加的消极情感状态，表现为焦虑样行为和烦躁不安，与 酗酒在之前的报告中，我们发现慢性间歇性乙醇暴露会导致 在BNST的5 HT系统中，一个与焦虑样行为相关的大脑区域。此外，我们还发现了一个 BNST中的5 HT敏感微电路调节焦虑样行为。我们建议在这里使用多个 聚合方法来测试酒精暴露对该5 HT敏感电路的离散方面的影响。 我们进一步建议探索这些过程的中断对酒精诱导的焦虑样焦虑的影响。 行为和饮酒。我们将检验中心假设，即慢性间歇性酒精暴露 导致BNST中的5-HT敏感回路持续适应，以驱动增加的焦虑样行为 和酒精消费。

Abstract Alcohol abuse is an enormous public health problem. While there have been significant gains in our knowledge of this disorder, we lack fundamental knowledge pertaining to the biological mechanisms that contribute to the chronic relapsing pathology of alcohol abuse. It has been hypothesized that alcohol exposure modifies function in brain regions critical for regulation of emotion, and that these changes underlie persistent alterations in behavior. The serotonin (5HT) system has been implicated in the pathophysiology of a range of psychiatric conditions, most notably anxiety disorders and depression (two conditions co-morbid with alcohol use disorders). Altered 5HT signaling has been suggested to contribute to cravings and relapses, as well as the increased negative affective state, manifested as the anxiety-like behavior and dysphoria, associated with alcohol abuse. In the previous submission, we found that chronic intermittent ethanol exposure drives changes in 5HT systems in the BNST, one brain region linked with anxiety-like behavior. Additionally, we identified a 5HT sensitive micro-circuit in the BNST that regulates anxiety-like behavior. We propose here to use multiple converging approaches to test the impact of alcohol exposure on discrete aspects of this 5HT sensitive circuit. We further propose to explore the impact of disruption of these processes on alcohol-induced anxiety-like behaviors and alcohol drinking. We will test the central hypothesis that chronic intermittent alcohol exposure leads to persistent adaptations in this 5HT sensitive circuit in the BNST to drive increased anxiety-like behavior and alcohol consumption.