The role of alternative polyadenylation in a mouse model of alcohol dependence

While APA is a frequent mechanism for regulating gene expression, it is especially consequential in neurons, where localized protein synthesis supports the activities of dendrites and axons. This localized protein synthesis is crucial for axon guidance and synaptic plasticity, forming the basis for learning and memory, key processes associated with the development of alcohol use disorder (AUD).

We investigated the role of APA in AUD using a mouse model of alcohol dependence, examining three brain regions in both sexes during protracted withdrawal, characterized by increased voluntary drinking after chronic intermittent ethanol (CIE) exposure. While we discovered APA changes in both sexes, our analysis revealed hundreds of genes undergoing APA in male but not female mice, indicating that these genes may contribute more to the CIE-induced escalation of ethanol consumption and dependence in males.