Project Summary Alcohol abuse, particularly binge alcohol (ethanol) drinking, is a major public health concern. Recent studies have revealed a high prevalence of binge drinking in adolescence and young adults. Like most drugs of abuse, ethanol use is usually initiated in adolescence leading to short-term as well as long-term negative health consequences, including increased risk for the development of alcohol use disorder (AUD). Although significant advances have been made in understanding the neurobiology of AUD, the effect of binge drinking on the brain and neuronal mechanisms contributing to the behavioral deficits are not yet clearly understood. Recent studies have suggested that an orphan G-protein-coupled receptor 55 (GPR55) signaling plays an important role in health and diseases. However, the role of GPR55 signaling in binge alcohol drinking is currently unknown. The proposed research is focused on understanding the effects of binge alcohol drinking in both adolescence and young adulthood on brain GPR55 signaling, and assess if the drugs targeted to GPR55 regulate binge ethanol drinking using a C57BL/6J mouse model. This study will provide further insight into neuronal mechanism of binge alcohol drinking, and the findings would assist in the development of effective therapeutic interventions for AUD.