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

Abstract

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. Female and male C57BL6/J mice had access to EtOH/water 2-bottle choice (2BC) 2h/d for 3weeks followed by exposure to EtOH vapor (vapor-2BC) or air for 5 cycles of 4days. An additional group never experienced EtOH (naïve). Mice were implanted with electroencephalographic (EEG) electrodes, and vigilance states were recorded across 24hours 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. Overall, vapor-2BC mice showed a decrease in the amount of SWS 4days 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. 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.