Chronic Ethanol Exposure Produces Sex-Dependent Impairments in Value Computations in the Striatum

Value-based decision-making relies on the striatum, where neural plasticity can be altered by chronic ethanol (EtOH) exposure, but the effects of such plasticity on striatal neural dynamics during decision-making remain unclear. This study investigated the long-term impacts of EtOH on reward-driven decision-making and striatal neurocomputations in male and female rats using a dynamic probabilistic reversal learning task. Following a prolonged withdrawal period, EtOH-exposed male rats exhibited deficits in adaptability and exploratory behavior, with aberrant outcome-driven value updating that heightened preference for chosen action. These behavioral changes were linked to altered neural activity in the dorsomedial striatum (DMS), where EtOH increased outcome-related encoding and decreased choice-related encoding. In contrast, female rats showed minimal behavioral changes with distinct EtOH-evoked alterations of neural activity, revealing significant sex differences in the impact of chronic EtOH. Our findings underscore the impact of chronic EtOH exposure on adaptive decision-making, revealing enduring changes in neurocomputational processes in the striatum underlying cognitive deficits that differ by sex.