Neural Basis of Ethanol Withdrawal-Induced Sleep Disturbance

项目总结

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.