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

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.