Neural Basis of Ethanol Withdrawal-Induced Sleep Disturbance

项目摘要 在人类和啮齿动物中，不正常的睡眠模式是过量饮酒的危险因素。 酒精依赖的受试者，在饮酒期间和戒断期间，都患有多种疾病。 睡眠中断在酒精戒断期间，恢复酒精依赖的患者通常会经历 严重和长期的睡眠中断，表现为严重的失眠沿着过度的白天 困倦酒精恢复期间的睡眠障碍会增加酒精使用复发的风险。 然而，负责调节乙醇对睡眠影响的神经机制在很大程度上仍然存在 未知基于最近的发现，我们假设反复接触酒精会扰乱睡眠 纹状体-基底前脑（NAc-BF）回路的模式，以性别依赖的方式。来测试我们 假设，我们将1）检查重复乙醇戒断对睡眠障碍模式的影响，2） 确定乙醇戒断诱导的睡眠障碍中NAc-BF回路的活性，以及3） 探讨NAc-BF回路操作在乙醇戒断诱导睡眠中的作用 扰动我们的研究将揭示NAc-BF回路如何促进慢性乙醇的神经基础- 引起睡眠障碍。我们期望在此过程中阐明性别依赖的睡眠障碍 酒精暴露。我们的研究结果将为未来R 01的关键研究奠定基础 研究发现和全面表征神经回路和分子机制 潜在的乙醇诱导的睡眠障碍，这可能会转化为临床研究，并确定新的 治疗目标

Project Summary In humans and rodents, abnormal sleep patterns are risk factors for excessive alcohol consumption. Alcohol-dependent subjects, both during a drinking period and during withdrawal, suffer from a multitude of sleep disruptions. During alcohol withdrawal, recovering alcohol-dependent patients commonly experience severe and protracted sleep disruptions manifested by profound insomnia along with excessive daytime sleepiness. Sleep disturbances during alcohol recovery can increase the risk of relapse to alcohol use. However, the neural mechanisms responsible for mediating the effects of ethanol on sleep remain largely unknown. Based on recent findings, we hypothesize that repeated ethanol exposure disrupts sleep patterns through the striato-basal forebrain (NAc-BF) circuit in sex-dependent manner. To test our hypothesis, we will 1) examine the effects of repeated ethanol-withdrawal on sleep disturbance patterns, 2) determine the activities of the NAc-BF circuit in ethanol withdrawal-induced sleep disturbance, and 3) Investigate the effects of the NAc-BF circuit manipulations in ethanol withdrawal-induced sleep disturbance. Our study will reveal neural basis of how NAc-BF circuits contribute to chronic ethanol- induced sleep disturbance. We expect to elucidate the sex-dependent sleep disturbance during the course of ethanol exposures. The outcomes of our study will be a critical research foundation for future R01 research to discover and comprehensively characterize neural circuits and molecular mechanisms underlying ethanol-induced sleep disturbance, which may translate into clinical studies and identify novel therapeutic targets.