Effects of aripiprazole on alcohol intake in an animal model of high-alcohol drinking

Aims: This study examined the effects of aripiprazole, a novel atypical antipsychotic drug with partial agonist properties at dopamine D2 receptors, on the voluntary limited access alcohol drinking of alcohol-preferring AA (Alko, Alcohol) rats. Methods: AA rats were taught to drink 10% alcohol in a 4 h limited access paradigm. Effects of acute aripiprazole (0, 0.3, 1.0, and 3.0 mg/kg) on the limited access alcohol drinking were studied. In repeated treatment experiment, aripiprazole (0, 1.0, and 6.0 mg/kg) was administered once daily over five successive days. To reveal any effect by aripiprazole not selective for alcohol drinking, 0.025% saccharin solution was substituted for alcohol during the 4 h limited access, and acute treatments were repeated. The effects of aripiprazole on ambulatory locomotor activity were tested with doses that were used in the acute experiments. Results: Acute aripiprazole at the doses of 0.3, 1.0, and 3.0 mg/kg had no effect on alcohol drinking. Repeated treatment with the aripiprazole dose of 6.0 mg/kg significantly diminished alcohol drinking at the 1 h time point. This dose had no effect on saccharin drinking when given acutely. Acute aripiprazole at the doses of 1.0, 3.0, and 6.0 mg/kg significantly suppressed locomotor activity. Conclusions: Aripiprazole decreased limited access alcohol drinking in AA rats, but only at a high dose that also strongly suppressed locomotor activity.