The antipsychotic aripiprazole antagonizes the ethanol- and amphetamine-induced locomotor stimulation in mice

Most drugs of abuse cause a locomotor stimulation, an effect, at least in part, mediated by increased accumbal dopamine (DA) overflow. Locomotor stimulation has been suggested to be a putative endophenotype for drug addiction. We therefore investigated the effects of aripiprazole, a partial DA D-2-receptor agonist, on ethanol as well as amphetamine-induced locomotor stimulation. In the present series of experiments, we found that aripiprazole (1.25 mg/kg, intraperitoneally [i.p.]) antagonized ethanol (1.75 g/kg, i.p.) as well as amphetamine (2 mg/kg, i.p.)induced locomotor stimulation in mice. We suggest that this effect might be related to aripiprazole's ability to alleviate drug-induced hyperdopaminergia without causing hypodopaminergia. Given that altered DA functions in drug dependence have been observed, it may be suggested that aripiprazole could be a new treatment strategy for treatment of drug dependence. (C) 2008 Elsevier Inc. All rights reserved.