Behavioral Core

项目总结 慢性酒精暴露的急性戒断与包括神经元在内的许多症状有关 过度兴奋，高度易怒，以及消极的情感状态。此外，急性戒断与 酒精消费升级和失控，这被认为至少部分是由于负面的 饮酒时的强化可以缓解戒断症状。大脑经历了显著的神经适应 在戒除长期酒精暴露期间。这些神经适应过程被认为起到了 在包括持续饮酒在内的不良适应行为中起着重要作用。在当前的 Funding Period Care调查人员发现了一些重要的、受表观遗传调控的变化 慢性酒精暴露戒断大鼠脑内基因表达的研究有趣的是，虽然有些人 戒断诱导的表观遗传修饰似乎在整个大脑中很常见，其中许多是大脑区域- 具体的。CARE研究人员进一步证明，这些表观遗传改变中的一些逆转 减轻戒断症状，包括与消极情绪和神经传递改变有关的症状。 然而，目前尚不清楚戒断诱导的表观遗传失调是否会促进酒精的升级。 消费。拟议的行为核心将允许护理调查人员通过提供 将戒断诱导的表观遗传学变化与饮酒行为改变联系起来所需的资源 CARE的所有四个研究项目。行为核心将为护理调查人员提供监督 测量操作者的标准化行为实验的设计、实施与分析 全身性或区域性乙醇戒断大鼠和对照大鼠的乙醇自我给药 逆转戒断引起的表观遗传学改变。行为核心还将促进集中 对照大鼠和慢性酒精流质饲料停喂大鼠的脑组织制作 由表观遗传学核心进行。由行为核心产生的结果将使护理调查人员 建立表观遗传修饰和酒精消费增加之间的因果联系。与.一起 每个研究项目的发现，这些数据将为未来旨在开发新药的工作提供信息 针对表观遗传因素治疗酒精使用障碍。

PROJECT SUMMARY Acute withdrawal from chronic alcohol exposure is associated with a number of symptoms including neuronal hyperexcitability, heightened irritability, and a negative affective state. In addition, acute withdrawal is associated with escalated and uncontrolled alcohol consumption, which is thought to occur, at least in part, due to negative reinforcement as drinking alleviates withdrawal symptoms. The brain undergoes significant neuroadaptations during withdrawal from chronic alcohol exposure. These neuroadaptive processes are thought to play an important role in driving maladaptive behaviors including continued alcohol consumption. During the current funding period CARE investigators have uncovered a number of significant, epigenetically regulated changes in gene expression in the brains of rats withdrawn from chronic ethanol exposure. Interestingly, while some withdrawal-induced epigenetic modifications appear to be common throughout the brain, many are brain region- specific. CARE investigators have further demonstrated that reversal of some of these epigenetic alterations attenuates withdrawal symptoms including those associated with negative affect and altered neurotransmission. However, it is not yet known whether withdrawal-induced epigenetic dysregulation promotes escalated alcohol consumption. The proposed Behavioral Core will allow CARE investigators to address this gap by providing the resources necessary to link withdrawal-induced epigenetic changes with alterations in drinking behavior across all four Research Projects of the CARE. The Behavioral Core will provide CARE investigators with oversight of experimental design, implementation, and analysis of standardized behavioral experiments measuring operant ethanol self-administration in control and ethanol withdrawn rats following either systemic or region-specific reversal of withdrawal-induced epigenetic alterations. The Behavioral Core will also facilitate centralized production of brain tissue from control rats and rats withdrawn from chronic ethanol liquid diet for experiments conducted by the Epigenetics Core. The results generated by the Behavioral Core will allow CARE investigators to establish a causal link between epigenetic modifications and escalated alcohol consumption. Together with findings from each Research Project, these data will inform future work aimed at the development of novel drugs targeting epigenetic factors for the treatment of alcohol use disorders.