Metabolic control of cue reactivity during alcohol withdrawal

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PROJECT SUMMARY Alcohol use disorder (AUD) is one of the most prevalent psychiatric disorders in the United States. Chronic alcohol consumption in individuals with AUD is associated with lowered glucose metabolism and increased acetate metabolism in the brain. Following abrupt cessation of alcohol consumption, sudden decreases in acetate may cause the brain to become “energy-deprived”, which could induce heightened craving and symptoms of withdrawal. The main goal of this proposal is to test the hypothesis that energy deprivation during withdrawal contributes to alcohol craving by influencing reward-encoding neural circuitry. Analyses for Specific Aim 1 will focus on defining the impact of altered brain metabolism in the dorsal anterior cingulate cortex (dACC) on its connectivity with the ventral striatum (VS) and on specifying the role of connectivity between the dACC and VS in facilitating whole-brain transitions to alcohol cue-induced neural activity states. Analyses for Specific Aim 2 will seek to define the relationship between metabolic function in the dACC, its role in driving whole-brain dynamics, and alcohol craving. Completion of this proposal will provide a framework for predicting the impact of metabolic interventions on brain state and craving, which will aid the development of therapeutic approaches for AUD.