The impact of intermittent exercise on mouse ethanol drinking and abstinence-associated affective behavior and physiology

Background Negative emotional states are associated with initiating and maintaining alcohol use and driving relapse in withdrawal and protracted abstinence. Physical exercise is correlated with decreased negative affective symptoms, although the direct relationship between drinking patterns and relative exercise has not been fully elucidated. Methods We incorporated intermittent running wheel access into a chronic continuous access two-bottle choice ethanol drinking model in female C57BL/6J mice. Wheel access was granted intermittently once mice established a preference for ethanol over water. After six weeks, ethanol was removed (forced abstinence) and mice were given continuously unlocked or locked wheels. Negative affect-like behavior, home cage behavior, and metabolic activity were measured in protracted abstinence. Results Wheel access shifted drinking patterns in mice, increasing drinking when the wheel is locked, and decreasing drinking when unlocked. Moreover, ethanol preference and consumption showed a strong negative correlation with the amount of running. We next assessed negative affect-like behavior in abstinence via the novelty suppressed feeding and saccharin preference tests. Unlimited wheel access mitigated abstinence-induced latency increases. Mice in abstinence also spent more time sleeping during the active dark cycle than control mice, providing more evidence for abstinence-induced anhedonia- and depression-like behavior. Furthermore, running wheel access in abstinence decreased dark cycle sleep to comparable ethanol- and wheel-naive mice. Given the positive impact of exercise- and the negative impact of alcohol- on metabolic health, we compared metabolic phenotypes of ethanol-abstinent mice with and without wheel access. Wheel access increased energy expenditure, carbon dioxide production, and oxygen consumption, providing a potential metabolic mechanism through which wheel access improves affective state. Conclusions This study suggests including exercise into existing AUD treatment regimens has the potential to reduce drinking, improve affective state in abstinence and may serve as a viable non-pharmacological approach to prevent the development of an AUD in high-risk individuals.