Aripiprazole blocks reinstatement but not expression of morphine conditioned place preference in rats

Abstract

Aripiprazole is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D 2 receptors and serotonin-1A (5-hydroxytryptamine, 5-HT 1A) receptors and minimal side effects. Based on its pharmacological profile, including stabilization of mesocorticolimbic DA activity (a pathway implicated in drug addiction), we investigated the effects of aripiprazole on relapse to morphine seeking in rats. In experiment 1, rats underwent morphine-induced conditioned place preference (CPP) training with alternate injections of morphine (5 mg/kg, s.c.) and saline (1 ml/kg, s.c.) for 8 consecutive days. To examine the effect of aripiprazole on the expression of morphine-induced CPP, rats received aripiprazole (0, 0.03, 0.1, and 0.3 mg/kg, i.p.) 30 min before testing for the expression of CPP. In experiment 2, rats underwent the same CPP training as in experiment 1 and subsequent extinction training. To examine the effect of aripiprazole on reinstatement of morphine-induced CPP, rats received aripiprazole 30 min before testing for reinstatement of CPP. In experiment 3, to assess the effects of aripiprazole on locomotor activity, aripiprazole was administered 30 min before testing for locomotor activity. Aripiprazole significantly decreased the reinstatement of CPP induced by a priming injection of morphine but had no effect on the expression of morphine-induced CPP or locomotor activity. The D 2 and 5-HT 1A partial agonist and 5-HT 2A antagonist properties of aripiprazole likely account for the blockade of relapse to drug seeking. These findings suggest that aripiprazole may have therapeutic value for reducing craving and preventing relapse to drug seeking.