Neural Basis of Ethanol Withdrawal-Induced Sleep Disturbance

项目摘要 在人类和啮齿动物中，异常的睡眠模式是过度饮酒的风险因素。 酒精依赖的受试者，无论是在饮酒期间还是戒酒期间，都会遭受大量的 睡眠障碍。在戒酒期间，正在康复的酒精依赖患者通常会经历 严重和长期的睡眠中断，表现为严重失眠和白天过多 困倦。酒精恢复过程中的睡眠障碍会增加再次饮酒的风险。 然而，负责调节酒精对睡眠影响的神经机制在很大程度上仍然存在。 未知。根据最近的发现，我们假设反复接触酒精会扰乱睡眠 纹状体-基底前脑(NAC-BF)环路的模式与性别有关。测试我们的 假设，我们将1)检查反复戒酒对睡眠障碍模式的影响，2) 在酒精戒断引起的睡眠障碍中测定NAC-BF回路的活动，以及3) NAC-BF环路操作在酒精戒断睡眠中的作用 骚乱。我们的研究将揭示NAC-BF回路如何参与慢性乙醇的神经基础- 诱发睡眠障碍。我们希望在此过程中阐明性别依赖性睡眠障碍。 暴露在酒精环境中。我们的研究结果将成为未来R01的重要研究基础 发现和综合表征神经回路和分子机制的研究 潜在的酒精诱导的睡眠障碍，这可能转化为临床研究并识别新的 治疗靶点。

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.