Dorsomedial striatal AMPA receptor antagonism increases alcohol binge drinking in selectively bred crossed high alcohol preferring mice

Crossed high alcohol preferring (cHAP) mice have been selectively bred to consume considerable amounts of alcohol resulting in binge drinking. The dorsomedial striatum (DMS) is a brain region involved in goal‐directed action selection, and dorsolateral striatum (DLS) is a brain region 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 hypothesised 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 2 h each day for 11 days. Mice were microinjected with the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid 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 the DMS and DLS 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 dorsal striatal subregions. Together, these findings suggest that glutamatergic activity in the DMS may serve to limit binge drinking in cHAP mice. AMPA receptor antagonism in the dorsomedial striatum of selectively bred high alcohol preferring mice causes an increase in binge alcohol drinking. AMPA receptor antagonism in the dorsolateral striatum of selectively bred high alcohol preferring mice does not alter binge alcohol drinking. This effect may be because of innate AMPA receptor ratio differences between the dorsal striatal subregions.