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Research ArticleBehavioral Pharmacology

Effects of Dopamine D2/D3 Receptor Ligands on Food-Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

Paul W. Czoty and Michael A. Nader
Journal of Pharmacology and Experimental Therapeutics February 2013, 344 (2) 329-338; DOI: https://doi.org/10.1124/jpet.112.201012
Paul W. Czoty
Departments of Physiology and Pharmacology (P.W.C., M.A.N.) and Radiology (M.A.N.), Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Michael A. Nader
Departments of Physiology and Pharmacology (P.W.C., M.A.N.) and Radiology (M.A.N.), Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Abstract

Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence. The present experiments examined the effect of acute and repeated administration of drugs with varying intrinsic efficacy at D2/D3 receptors on the relative reinforcing strength of cocaine. Use of socially housed cynomolgus monkeys permitted the assessment of whether social status, known to alter D2/D3 receptor availability, influenced the behavioral effects of D2/D3 receptor compounds. The high-efficacy agonist R(−)−norpropylapomorphine [(−)−NPA], low-efficacy agonist aripiprazole (ARI), and antagonist eticlopride (ETIC) were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine self-administration dose-effect curve was determined daily. The effects of 5-day treatment with ARI and (−)−NPA were characterized under conditions in which monkeys did (ARI) or did not [ARI and (−)−NPA] self-administer cocaine during treatment. When administered acutely, ARI and ETIC increased the choice of low cocaine doses, and only (−)−NPA decreased the choice of higher cocaine doses and cocaine intake; effects were similar across social ranks. When administered repeatedly while self administration occurred only on days 1 and 5 of treatment, ARI, but not (−)−NPA, decreased cocaine choice in dominant monkeys, whereas (−)−NPA, but not ARI, did so in subordinates. When dominant monkeys self-administered cocaine on all five days of ARI treatment, however, these effects were not observed. The results indicate that the behavioral effects of D2/D3 receptor agonists can differ according to intrinsic efficacy and subject characteristics. Moreover, these results suggest that exposure to cocaine during treatment can counteract treatment-induced reductions in the reinforcing effects of cocaine.

Footnotes

  • The research described in this manuscript was supported by grants from the National Institutes of Health National Institute on Drug Abuse [DA 10584 and DA 12460].

  • dx.doi.org/10.1124/jpet.112.201012.

  • Received October 10, 2012.
  • Accepted December 3, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 344 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 344, Issue 2
1 Feb 2013
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Research ArticleBehavioral Pharmacology

Dopamine D2/D3 Receptor Drugs and Cocaine Choice

Paul W. Czoty and Michael A. Nader
Journal of Pharmacology and Experimental Therapeutics February 1, 2013, 344 (2) 329-338; DOI: https://doi.org/10.1124/jpet.112.201012

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Research ArticleBehavioral Pharmacology

Dopamine D2/D3 Receptor Drugs and Cocaine Choice

Paul W. Czoty and Michael A. Nader
Journal of Pharmacology and Experimental Therapeutics February 1, 2013, 344 (2) 329-338; DOI: https://doi.org/10.1124/jpet.112.201012
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