Efficacy of the atypical antipsychotic aripiprazole in d-amphetamine-based preclinical models of mania

The atypical antipsychotic aripiprazole has been demonstrated to reduce symptoms of bipolar mania. To further profile the antimanic-like properties of aripiprazole in relevant preclinical models, we examined its efficacy in d-amphetamine-based behavioural models of acute mania in rats. The effects of acute and repeated administration of aripiprazole were assessed in the facilitation of intracranial self-stimulation (ICSS) and hyperlocomotion after acute d-amphetamine, and in the sensitized facilitation of ICSS function and hyperlocomotion after repeated d-amphetamine. Acutely, aripiprazole (0.75, 1.5 and 2.5 mg/kg i.p.) increased ICSS thresholds, attenuated the reward-facilitating effects of d-amphetamine (0.5 mg/kg i.p.), decreased motor activity and prevented d-amphetamine-induced hyperlocomotion. Co-administration of aripiprazole and d-amphetamine for 7 d resulted in aripiprazole counteracting the d-amphetamine-induced sensitization in facilitation of brain reward function and hyperlocomotion. These results indicate the efficacy of aripiprazole in d-amphetamine-based preclinical models of acute mania that are characterized by increased motivational drive and/or hyperfunction of brain reward.