Bupropion, Alone and in Combination with Naltrexone, Blunts Binge‐Like Ethanol Drinking and Intake Following Chronic Intermittent Access to Ethanol in Male C57BL/6J Mice

Background Regular binge drinking is associated with numerous adverse consequences, yet the U.S. Food and Drug Administration (FDA) has approved only 4 medications for the treatment of alcohol use disorders, and none have been specifically targeted for treating binge drinking. Here, we assessed the effectiveness of the dopamine/norepinephrine re‐uptake inhibitor, bupropion (BUP), alone and in combination with naltrexone (NAL), to reduce binge‐like and chronic ethanol (EtOH) intake in mice. While BUP is an FDA‐approved drug that is currently used to treat depression and nicotine dependence, there has been only limited investigation to assess the ability of BUP to reduce EtOH intake. Methods Male C57BL/6J mice were tested with 20% (v/v) EtOH using “drinking in the dark” (DID) procedures to model binge‐like EtOH intake and following intermittent access to EtOH (IAE). In Experiment 1, mice were given intraperitoneal (i.p.) injection of 0, 20, or 40 mg/kg BUP 30 minutes before DID testing; in Experiment 2, mice were given i.p. injection of vehicle, BUP (20 mg/kg), NAL (3 mg/kg), or BUP + NAL (20 and 3 mg/kg, respectively) 30 minutes before DID testing; and in Experiment 3, mice were given i.p. injection of 0, 20, 40, or 60 mg/kg BUP 30 minutes before EtOH access after mice had 16 weeks of IAE. Results BUP dose dependently blunted EtOH intake with DID procedures and after 16 weeks of IAE. Administration of subthreshold doses of BUP + NAL also reduced binge‐like EtOH intake. Finally, BUP failed to reduce consumption of a 3% (w/v) sucrose solution. Conclusions BUP, alone and in combination with NAL, may represent a novel approach to treating binge EtOH intake. We are currently assessing the efficacy of BUP to curb binge drinking in a phase II clinical trial experiment. Bupropion (BUP), a dopamine/norepinephrine re‐uptake inhibitor and an activator of proopiomelanocortin signaling, has been used clinically to treat depression, smoking addiction, and eating disorder. Here we show that BUP, alone and in combination with naltrexone, reduces binge‐like ethanol consumption in male mice. These data suggest that BUP may represent a novel approach to treating binge ethanol intake, which we are currently assessing in a Phase II clinical trial experiment.