Acute docosahexaenoic acid administration reduces binge-like ethanol consumption and palatable substances in C57BL/6J mice

Abstract

Introduction Excessive alcohol consumption, particularly binge drinking, is associated with cognitive impairments, emotional dysregulation and an increased vulnerability to alcohol use disorders. Emerging evidence suggests that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, modulates neuroinflammatory processes and influences dopaminergic signaling involved in reward-related behaviors. However, its acute effect on binge-like consumption remains poorly understood. The present study investigated the effects of acute oral administration of DHA-rich fish oil on binge-like drinking of ethanol in male and female C57BL/6J mice, utilizing caloric and non-caloric reinforcers to evaluate behavioral specificity. Methods Using the Drinking-in-the-Dark (DID) paradigm, voluntary intake of ethanol, sucrose and saccharin were evaluated following DHA administration. To control potential confounds, spontaneous locomotor activity and anxiety-like behavior were assessed. Results Acute DHA administration significantly reduced binge-like consumption of ethanol in both sexes, with a parallel reduction observed in sucrose and saccharin intake. Importantly, DHA did not alter locomotor activity or anxiety-like behaviors. Conclusion These findings suggest that DHA exerts a rapid and robust dampening effect on binge consumption of both ethanol and natural rewards, supporting a potential role of DHA in modulating reward-driven intake. Collectively, this study highlights DHA as a promising candidate modulator of neurobehavioral processes associated with excessive and non-homeostatic consumption.