Dorsomedial Striatal Glutamatergic Transmission Inhibits Binge Drinking in Selectively Bred Crossed High Alcohol Preferring Mice

Abstract

AbstractCrossed high alcohol preferring (cHAP) mice have been selectively bred to consume considerable amounts of alcohol resulting in binge drinking. The dorsal striatum (DS) is a brain region involved in action selection where the dorsomedial striatum (DMS) is involved in goal-directed action selection and dorsolateral striatum (DLS) is involved in habitual action selection. Alcohol use disorder (AUD) may involve a disruption in the balance between the DMS and DLS. While the DLS is involved in binge drinking, the reliance on the DMS and DLS in binge drinking has not been investigated in cHAP mice. We have previously demonstrated that glutamatergic activity in the DLS is necessary for binge-like alcohol drinking in C57BL/6J mice, another high drinking mouse. Because of this, we hypothesized that DLS glutamatergic activity would gate binge-like alcohol drinking in cHAP mice. cHAP mice underwent bilateral cannulation into the DMS or DLS and were allowed free-access to 20% alcohol for two-hours each day for 11 days. Mice were microinjected with the AMPA receptor (AMPAR) antagonist, NBQX, into the DMS or DLS immediately prior to alcohol access. AMPAR protein expression was also assessed in a separate group of animals in DS subregions following an 11-day drinking history. We found that intra-DMS (but not intra-DLS) NBQX, alters binge alcohol drinking, with intra-DMS NBQX increasing alcohol consumption. We also found that the ratio of GluA1 to GluA2 differs across DS subregions. Together, these findings suggest that glutamatergic activity in the DMS may serve to limit binge drinking in cHAP mice.