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Research ArticleArticle

Characterization of the Effects of the Partial Dopamine Agonist Terguride on Cocaine Self-Administration in the Rat

Luigi Pulvirenti, Claudia Balducci, Marla Piercy and George F. Koob
Journal of Pharmacology and Experimental Therapeutics September 1998, 286 (3) 1231-1238;
Luigi Pulvirenti
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Claudia Balducci
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Marla Piercy
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George F. Koob
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Abstract

Dopamine neurotransmission is an important neuropharmacological component of cocaine self-administration in rodents. Terguride is a prototype drug belonging to a recently characterized class of compounds, dopamine partial agonists, which appear to possess a unique pharmacological profile in altering dopamine neurotransmission, where these drugs act as antagonists in conditions of high dopaminergic tone. The aim of the present study was therefore to test the effects of systemic administration of terguride in rats self-administering cocaine intravenously. The different aspects of cocaine self-administration examined after treatment with terguride were (a) the acute reinforcing properties of cocaine in rats exposed to limited-access self-administration of cocaine, (b) a full cocaine dose-effect function, (c) the reinforcing properties of cocaine as measured by a progressive ratio schedule and (d) the ability of terguride to maintain self-administration by itself. Terguride (0.025–0.4 mg/kg i.p.) significantly and dose-dependently reduced the acute reinforcing properties of cocaine as measured by an increase in responding for a single training dose of cocaine and a reduction of the inter-reinforcement interval. In addition, terguride (0.2–0.4 mg/kg) shifted the entire cocaine dose-effect function to the right, thus showing an antagonism of the reinforcing properties of cocaine independent of response rate. Moreover, in rats trained to self-administer cocaine on a progressive ratio schedule, terguride reduced the maximum fixed ratio (“breaking point”) for cocaine reinforcement, also suggesting a decrease in the reinforcing properties of cocaine. Finally, in rats trained to self-administer cocaine terguride did not substitute for cocaine, thus indicating that terguride does not maintain intravenous self-administration by itself.

Footnotes

  • Send reprint requests to: Luigi Pulvirenti, M.D., Department of Neuropharmacology CVN-7, The Scripps Research Institute, 10666 No. Torrey Pines Rd., La Jolla, CA 92037.

  • ↵1 This work was partially supported by Nida grants D. A.-04398 and D. A.-08467 and by a Fellowship from the “C. Mondino” Foundation (L. P.). This is manuscript number 10309-NP of The Scripps Research Institute.

  • Abbreviations:
    FR
    fixed ratio
    ANOVA
    analysis of variance
    i.p.
    intraperitoneal
    IV
    intravenous
    • Received December 4, 1997.
    • Accepted May 4, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 286, Issue 3
1 Sep 1998
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Research ArticleArticle

Characterization of the Effects of the Partial Dopamine Agonist Terguride on Cocaine Self-Administration in the Rat

Luigi Pulvirenti, Claudia Balducci, Marla Piercy and George F. Koob
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1231-1238;

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Research ArticleArticle

Characterization of the Effects of the Partial Dopamine Agonist Terguride on Cocaine Self-Administration in the Rat

Luigi Pulvirenti, Claudia Balducci, Marla Piercy and George F. Koob
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1231-1238;
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