Voluntary wheel-running reduces harmful drinking in a genetic risk model for drinking to intoxication

Abstract

Physical activity (PA) may provide an effective and equitable treatment option for addressing the harm associated with Alcohol Use Disorders (AUDs). Wheel-running (WR) – a well characterized rodent model of PA – reduces intake and craving for many drugs of abuse; however, its effects on models of harmful ethanol intake are mixed. This may in part be due to critical differences in drinking paradigm, genetics background, chronicity of ethanol, and the modality and duration of PA being tested. To compliment and extend prior work, we evaluated whether key stages of PA development would differentially reduce binge-like ethanol drinking in inbred High Drinking in the Dark (iHDID-1) mice, a unique genetic risk model for drinking to intoxication. AUD is a chronic, relapsing disorder. To better reflect this condition, adult female and male iHDID-1 mice underwent a chronic (4-weeks) “Drinking in the Dark” (DID) protocol – a model of binge-like ethanol drinking - along with a locked running (to control for the effect of novelty). Early stages of PA evoke much higher signs of physiological and neurological stress than more chronic, habitual stages of PA. Therefore, we tested whether acute WR (1-week) altered ethanol intake differently than chronic WR (4-weeks). Here, we found that both acute and chronic WR reduced ethanol intake in female and male iHDID-1 mice. To evaluate whether the effect of PA was specific to ethanol, we further tested whether acute WR reduced water intake in the DID protocol. Analysis revealed that male WR iHDID-1 mice had greater water intake than wheel-locked controls. Moreover, WR during the time of DID was positively correlated with water intake, but not ethanol intake, suggesting WR and DID are not competing behaviors. Taken together, these findings offer support for the role of PA as a meaningful intervention strategy for reducing harmful drinking and emphasize the need to explore the underlying neurobiological mechanisms as a means of guiding PA as an adjunctive therapy for AUD.