Changes in activity across the light-dark cycle during ethanol self-administration, extinction, and ethanol cue-induced reinstatement in rats

Alcohol use disorder (AUD) patients have a high prevalence of sleep disturbances and report disrupted sleep as a contributor to relapse. Studies are needed to understand the development and progression of sleep problems throughout the AUD cycle. This study tracked activity across the light-dark cycle as a measure of sleep-related endpoints in rats during ethanol self-administration, extinction of self-administration, and ethanol cue-induced reinstatement. Male and female rats implanted with accelerometer-based telemetry devices were induced to drink ethanol using a sucrose-fade procedure. Then, ethanol-maintained behavior was extinguished. Alcohol seeking was reinstated by re-exposure to an ethanol-paired cue. Twenty-three hour actigrams were generated during baseline, acquisition of self-administration, extinction, and reinstatement. Compared to baseline, ethanol self-administration resulted in increased activity during the light (inactive) phase exclusively. During extinction, total activity was increased further during the light (inactive) phase, as well as in the dark (active) phase that preceded the next-day operant session. Inactivity measures during extinction, but not self-administration, negatively correlated with reinstatement responding. This study identified deleterious changes in activity/inactivity measures that reflect potential impairment in sleep-wake cycles during active ethanol self-administration and extinction of ethanol-seeking behavior. Further, disruptions in activity measures obtained from the extinction phase negatively impacted relapse-like behavior, such that greater disruptions in sleep-related behavior were associated with higher reinstatement rates. These findings support the idea of treating disrupted sleep, specifically during abstinence, as a means to reduce relapse in AUD patients.