Effects of aripiprazole on operant responding for a natural reward after psychostimulant withdrawal in rats.

RATIONALE: Withdrawal from repeated amphetamine administration has been shown to decrease the motivation to work for a natural reward in rats, a phenomenon thought to be associated with hypofunction of the mesolimbic dopamine system.

OBJECTIVES

We tested whether aripiprazole, a partial dopamine receptor agonist, can restore the animals' responding for reward pellets after amphetamine withdrawal.

MATERIALS AND

METHODS

Rats were trained to lever-press for food pellets under a progressive ratio-schedule of reinforcement. After reaching a stable breakpoint, i.e., the highest ratio completed, one group was injected ten times with increasing doses of amphetamine (1 to 10 mg/kg, three times a day for 4 days), while the other group received vehicle injections. The rats were again tested for their breakpoint 24 h after the last amphetamine injection under 0.0, 0.25, 0.75, and 2.5 mg/kg aripiprazole.

RESULTS

Withdrawal from repeated amphetamine injection reduced the breakpoint while low doses of aripiprazole (0.25 and 0.75 mg/kg) prevented this effect. In addition, the rats needed a longer time for the first 20 pellets (fixed ratio-schedule training before starting the progressive ratio-schedule) after amphetamine withdrawal but not after subsequent injection with aripiprazole. It is notable that the injection of 2.5 mg/kg aripiprazole reduced responding for reward pellets and prolonged the duration for the first 20 pellets irrespective of previous amphetamine or vehicle treatment. However, withdrawal from repeated administration of 0.25 and 2.5 mg/kg aripiprazole did not reduce responding for reward pellets.

CONCLUSIONS

These results suggest that aripiprazole may have potential use as a treatment for the motivational effects of the acute withdrawal stage of the psychostimulant addiction cycle.