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. Overall design: This study tests the effect of knocking out ACSS2 (an enzyme involved in alcohol metabolism in the brain) on alcohol drinking behavior in rodents. This series contains RNA-seq from WT or ACSS2 KO mice, including both males and females, who were subjected to the "drinking in the dark" experimental model for chronic alcohol use (see treatment protocol, below). Samples are from seven dissected portions of the brain: amygdala, cortex, dorsal & ventral hippocampus, prefrontal cortex, and dorsal & ventral striatum. The replicate structure is as follows. For female mice, there are three ACSS2 KO biological replicates each for all brain regions, while the number of WT biological replicates is either two or three depending on the brain region (amygdala, cortex, and prefrontal cortex have two replicates each while dorsal and ventral hippcampus and dorsal and ventral striatum have three replicates each). For male mice, there are three biological replicates each of ACSS2 KO and WT for all tissues except prefrontal cortex, which has one ACSS2 KO and two WT.