ACSS2 drives drinking indulgence in male mice by coordinating a gene expression program in the ventral striatum

We recently established ACSS2 as a potential candidate for therapeutic interventions in alcohol use disorders (AUD), in which memory of alcohol-associated environmental cues is a primary driver of craving and relapse. Prior research, however, has been limited to passive exposure to ethanol and the importance of this pathway in models of voluntary drinking that better approximate human alcohol consumption remains unknown. Therefore, we assessed the effect of genetic ACSS2 inhibition on voluntary alcohol intake and simultaneously assayed the epigenetic and transcriptional changes that accompany alcohol consumption.