Attenuation of reinforcing and psychomotor stimulant effects of amphetamine by aripiprazole

Partial dopamine agonists are potential medications for the treatment of amphetamine addiction. They have been hypothesized to stabilize the dopamine system by acting as antagonists during high dopaminergic tone resulting from amphetamine use and as agonists during withdrawal. Aripiprazole is an atypical antipsychotic that acts as a partial D2 dopamine and a serotonin 5-HT(1A) agonist and a serotonin 5-HT(2A) antagonist. The aim of the present study was to examine the effects of aripiprazole on behaviors induced and maintained by d-amphetamine. To this end, intravenous d-amphetamine self-administration [fixed ratio 3 (FR3) schedule, 0.02 mg/infusion] and d-amphetamine-induced (0, 1.5 mg/kg intraperitoneally) locomotor activity, as well as spontaneous locomotor activity and sucrose pellet self-administration (FR3 schedule) were studied in male Wistar rats after aripiprazole (0, 0.3, 1, 3 mg/kg i.p.) administration. Aripiprazole pre-treatment resulted in bidirectional effects on amphetamine self-administration. The 1 mg/kg dose increased, and the highest dose decreased the number of amphetamine infusions. In the locomotor activity experiments, aripiprazole attenuated amphetamine-induced activity dose-dependently and tended to suppress spontaneous activity. The highest aripiprazole doses decreased also sucrose pellet self-administration. The increase in amphetamine self-administration with the intermediate aripiprazole dose, as well as the decrease in amphetamine-induced locomotor activity, suggests that aripiprazole acted as a dopamine antagonist. Suppression of amphetamine and sucrose self-administration by the highest aripiprazole dose was probably caused by non-specific effects. Together, these results indicate that under conditions of dopaminergic stimulation, aripiprazole attenuates the reinforcing and psychomotor stimulant effects of d-amphetamine, but the dose range for this effect is rather limited.