Systemic Administration of the AMPA Receptor Antagonist, NBQX, Reduces Alcohol Drinking in Male C57BL/6J, But Not Female C57BL/6J or High‐Alcohol‐Preferring, Mice

Abstract

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are ionotropic glutamate receptors that have been investigated for their role in modulating alcohol consumption. However, little is known about the role of AMPA receptors in the control of binge-like or free-access alcohol drinking in C57BL/6J or in selectively bred high-alcohol-preferring (HAP) mice. The purpose of this experiment was to assess the role of systemic administration of the AMPA receptor antagonist, 2,3-dioxo-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), on alcohol consumption using a model of binge-like drinking, drinking in the dark (DID) and free-access 2-bottle choice (2BC) in male and female C57BL/6J and HAP mice. C57BL/6J mice were allowed free access to 20% (v/v) alcohol for 2hours each day beginning 3hours into the dark cycle for 4days. On day 5, mice were intraperitoneally injected with one of 4 doses of NBQX (0, 3, 10, or 30mg/kg; n=10) 15minutes before alcohol presentation and were given 4-hour alcohol access (extended DID). HAP mice were given 24-hour free access to 10% (v/v) alcohol and water for 19days. On day 20, mice were intraperitoneally injected with one of 4 doses of NBQX (0, 3, 10, or 30mg/kg; n=9) 15minutes before alcohol and water presentation. In the first 2hours of DID, at 30mg/kg, male, but not female C57BL/6J or HAP, mice drank significantly less alcohol compared with controls and 30mg/kg NBQX did not alter saccharin intake in the males. Although male HAP mice drank significantly less alcohol than female mice following 10mg/kg NBQX, neither sex exhibited drinking that differed significantly from controls. NBQX did not reduce locomotor behavior at any dose, sex, or genotype. These data suggest that AMPA receptors play a key role in modulating binge-like alcohol consumption without altering saccharin consumption or general locomotion and that this effect is specific to sex and genotype.