Exercise (Wheel-Running) Reduces Chronic Alcohol-Induced Escalation of Drinking in Mice via Elevated BDNF-TrkB Receptor Activity

Abstract Alcohol use disorder (AUD) is a significant medical problem and there is great need for developing effective treatment strategies. Brain-Derived Neurotrophic Factor (BDNF) has been shown to play a role in regulating numerous pharmacological and motivational effects of alcohol. We have shown that chronic alcohol-induced escalation of drinking is accompanied by a deficit in BDNF levels in medial prefrontal cortex (mPFC). This study examined whether exercise (wheel-running) attenuates excessive alcohol drinking via increased BDNF expression, thereby mitigating the deficit in mPFC. Adult male C57BL/6J mice were given scheduled (2-hr/day) access to a running wheel in the home-cage 1-hr following opportunity to drink alcohol for 2-hr/day. After six weeks, mice were further separated into groups that received chronic alcohol vapor or control (air) inhalation exposure. Results indicated that alcohol consumption did not alter wheel-running and exercise did not alter alcohol intake during the 6-week baseline. Exercise increased BDNF mRNA and protein expression in mPFC, reversed chronic alcohol-induced reduction in BDNF levels, and attenuated escalated alcohol drinking. Systemic administration of a TrkB receptor antagonist (ANA-12) reversed the beneficial effects of wheel-running in the model. Together, these data provide support for exercise as a potentially effective intervention strategy for treating AUD.