1. ¹Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, USA
2. ²Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, KY, USA
3. ³Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, KY, USA
4. ⁴Department of Anatomy and Neurobiology, College of Medicine, University of Kentucky, Lexington, KY, USA
5. ⁵Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, KY, USA
6. ⁶Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA

Correspondence: Dr CR Rush, Department of Behavioral Science, University of Kentucky, Lexington, KY 40536-0086, USA. Tel: +1 859 323 6130, Fax: +1 859 323 5350, E-mail: crush2@uky.edu

Received 24 February 2005; Revised 22 April 2005; Accepted 16 May 2005; Published online 29 June 2005.

Abstract

The results of animal research suggest that the use of partial agonists at dopamine (DA) D₂ receptors may be an effective strategy for the treatment of stimulant dependence. Aripiprazole is an atypical antipsychotic that has partial agonist activity at D₂ receptors. In this experiment, seven human participants with a history of nontherapeutic stimulant use learned to discriminate 15 mg oral D-amphetamine. After acquiring the discrimination (ie 80% correct responding on four consecutive sessions), the effects of a range of doses of D-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with aripiprazole (0 and 20 mg), were assessed. D-Amphetamine alone functioned as a discriminative stimulus, produced prototypical subject-rated drug effects (eg increased ratings of Active, Alert, Energetic) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion D-amphetamine-appropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of D-amphetamine, as well as some of the subject-rated drug effects. These data are consistent with previous preclinical findings and suggest that DA partial agonists deserve further evaluation as potential pharmacotherapies in the management of stimulant dependence. Future studies should investigate the ability of aripiprazole or related compounds to attenuate the behavioral effects of stimulants associated with a greater degree of dependence, such as methamphetamine or cocaine, in dependent individuals.