Effects of Withdrawal from Chronic Intermittent Ethanol Exposure on Sleep Characteristics of Female and Male Mice

Background Sleep disruptions are an important consequence of alcohol use disorders. There is a dearth of preclinical studies examining sex differences in sleep patterns associated with ethanol (EtOH) dependence despite documented sex differences in alcohol‐related behaviors and withdrawal symptoms. The purpose of this study was to investigate the effects of chronic intermittent EtOH on sleep characteristics in female and male mice. Methods Female and male C57BL6/J mice had access to EtOH/water 2‐bottle choice (2BC) 2 h/d for 3 weeks followed by exposure to EtOH vapor (vapor‐2BC) or air for 5 cycles of 4 days. An additional group never experienced EtOH (naïve). Mice were implanted with electroencephalographic (EEG) electrodes, and vigilance states were recorded across 24 hours on the fourth day of withdrawal. The amounts of wakefulness, slow‐wave sleep (SWS), and rapid eye movement sleep were calculated, and spectral analysis was performed by fast Fourier transformation. Results Overall, vapor‐2BC mice showed a decrease in the amount of SWS 4 days into withdrawal as well as a decrease in the power density of slow waves, indicating disruptions in both the amount and quality of sleep in EtOH‐dependent mice. This was associated with a decrease in duration and an increase in number of SWS episodes in males and an increase in latency to sleep in females. Conclusions Our results revealed overall deficits in sleep regulation in EtOH‐dependent mice of both sexes. Female mice appeared to be more affected with regard to the triggering of sleep, while male mice appeared more sensitive to disruptions in the maintenance of sleep. In addition to escalation of ethanol drinking associated with chronic intermittent ethanol vapor exposure, male and female C57BL/6J mice showed altered sleep characteristics. This figure shows decreased sleep quantity and we also observed a reduction in delta power during sleep, consistent with reduced sleep quality. There were subtle sex differences in sleep latencies and episode features. Because sleep disturbances are considered so important in continued ethanol drinking and relapse, this model will be of great importance in examining possible treatments.