Aripiprazole attenuates the discriminative-stimulus and subject-rated effects of d-amphetamine in humans

Joshua A. Lile, William W. Stoops, Andrea R. Vansickel, Paul E.A. Glaser, Lon R. Hays, Craig R. Rush

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


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.

Original languageEnglish
Pages (from-to)2103-2114
Number of pages12
Issue number11
StatePublished - Nov 2005

Bibliographical note

Funding Information:
A National Institute on Drug Abuse Grant DA 10325 (CRR) supported this research. *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: [email protected] Received 24 February 2005; revised 22 April 2005; accepted 16 May 2005 Online publication: 24 May 2005 at Npp052405050126/default.pdf


  • Aripiprazole
  • D-amphetamine
  • Drug discrimination
  • Partial agonist
  • Psychomotor performance
  • Subjective effects

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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