Aripiprazole and topiramate, alone or in combination, block the expression of ethanol-induced conditioned place preference in mice

•Ethanol induced conditioned place preference (CPP) in male mice.•Treatment with topiramate (Top) blocked the expression of ethanol-induced CPP.•Treatment with aripiprazole (Arip) blocked the expression of ethanol-induced CPP.•Combined treatment with ineffective doses of Top and Arip blocked CPP expression. Ethanol is the most largely consumed drug in the world. Because of its complex mechanisms of action, studies suggest that the combination of drugs with distinct pharmacological effects may be a promising alternative for treating ethanol use disorder. In the present study, we aimed to investigate the effects of topiramate, alone and in combination with aripiprazole, on ethanol-induced conditioned place preference (CPP). Adult male mice were conditioned with ethanol (1.8 g/kg, i.p.) in the conditioned place preference (CPP) apparatus. Animals were then treated with vehicle, topiramate (2.5, 5 or 10 mg/kg, i.p.), aripiprazole (0.025, 0.05, 0.075 or 0.1 mg/kg, i.p.) or a combination of subthreshold doses of topiramate and aripiprazole (5 and 0.075 mg/kg, respectively) in the ethanol-paired compartment for 8 consecutive days. The expression of ethanol-induced CPP was then evaluated during a drug-free test performed 24 h after a re-exposure to ethanol in the ethanol-paired compartment. Treatment with 10 mg/kg topiramate or 0.1 mg/kg aripiprazole blocked the expression of ethanol-induced CPP. Combined treatment with 5 mg/kg topiramate and 0.075 mg/kg aripiprazole, doses that alone were not effective, also blocked the expression of CPP to ethanol. Topiramate and aripiprazole, alone or in combination, blocked the expression of ethanol-induced CPP. By showing that a combination of lower, subthreshold doses or topiramate and aripiprazole was effective in blocking the conditioned reinforcing properties of the ethanol-paired environment in mice, our current findings provide important insights into the therapeutic use of these drugs in ethanol use disorder.