Enhancement of cue-induced reinstatement of alcohol seeking by acute total sleep restriction in male Wistar rats.

Clinical studies suggest that sleep impairment is a barrier to successful treatment in alcohol use disorder (AUD) patients, with sleep disruption associated with relapse to alcohol taking. To date, no preclinical study has evaluated the relationship between impaired sleep and alcohol relapse. In the present study, we used a self-administration model to investigate the effects of sleep restriction on reinstatement induced by alcohol-paired environmental cues. Using a sucrose fading protocol, male Wistar rats (N = 8) were trained to self-administer alcohol under a fixed-ratio 2 schedule of alcohol delivery such that completion of every second response resulted in the delivery of the alcohol solution and activation of the alcohol-paired cue light. Once self-administration was stable, behavior was extinguished by omitting delivery of the alcohol solution and the alcohol-paired cues. When responding reached low, stable levels, alcohol seeking was induced by re-presentation of the alcohol-paired cues but with no alcohol solution available for self-administration. To evaluate the effects of sleep restriction on cue-induced alcohol seeking, reinstatement tests were conducted after 6-h of total (slow wave + rapid eye movement [REM]) sleep restriction using the gentle handling method or after 6-h of REM sleep-only restriction using the flower pot method. Relevant control conditions also were evaluated. The results showed that acute restriction of total sleep, but not REM sleep primarily, significantly augmented cue-induced reinstatement of alcohol seeking. This increase was specific to total sleep restriction conditions and cannot be attributed to differences in alcohol intake, responding, or days to extinction. Our findings imply that acute slow wave sleep restriction is necessary and/or sufficient for the enhancement of cue-induced alcohol seeking and, further, suggest that decreased slow wave sleep in AUD patients places individuals at a unique risk for relapse.