Recent work has focused on how differences in genetics and intracellular signaling impact ethanol’s actions on microcircuits and the relationship between these effects and alcohol intoxication, reward, and drinking. It is well known that C57Bl6J mice differ from DBA mice in ethanol-related behaviors (Belknap et al., 1993), likely due to differences in genes governing the neural mechanisms underlying reward and aversion (Cunningham et al., 1992). A top-down examination of ethanol’s effects on GABAA-receptor-mediated transmission in cerebellar microcircuitry revealed differences between these strains that may account for the behavioral differences. Rossi and colleagues observed a differential balance between the GABA-potentiating and inhibiting effects of ethanol in C57Bl6J and DBA mouse strains (Kaplan et al., 2013) that correlate with differences in ethanol intake. More recent studies indicate that enhancing GABAergic transmission in the cerebellum of C57Bl6J mice decreases ethanol drinking to levels seen in DBA mice (Kaplan et al., 2016).
