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 D2-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.
Jerlhag
Elisabet
E
Institute of Neuroscience and Physiology, Department of Pharmacology, P.O. Box 431, SE-405 30 Göteborg, Göteborg University, Sweden. elisabet.jerlhag@pharm.gu.se
D000661:Amphetamine / Q000037:antagonists & inhibitors*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D000431:Ethanol / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000431:Ethanol; D000068180:Aripiprazole; D000661:Amphetamine