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Research ArticleNEUROPHARMACOLOGY

μ-Opioid Receptor Knockout Mice Do Not Self-Administer Alcohol ,

Amanda J. Roberts, Jeffrey S. McDonald, Charles J. Heyser, Brigitte L. Kieffer, Hans W. D. Matthes, George F. Koob and Lisa H. Gold
Journal of Pharmacology and Experimental Therapeutics June 2000, 293 (3) 1002-1008;
Amanda J. Roberts
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Jeffrey S. McDonald
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Charles J. Heyser
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Brigitte L. Kieffer
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Hans W. D. Matthes
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George F. Koob
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Lisa H. Gold
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Abstract

Opioid peptides long have been hypothesized to play a role in ethanol reinforcement. Neuropharmacological studies have shown that opioid receptor antagonists decrease ethanol self-administration in rodents and prevent relapse in humans. However, the exact mechanism for such powerful effects has remained elusive. The availability of μ-opioid receptor knockout mice has made possible the direct examination of the role of the μ-opioid receptor in mediating ethanol self-administration. In the present experiments, both nosepoke and lever operant ethanol self-administration and several tests of two bottle-choice ethanol drinking were studied in these genetically engineered mice. In no case did knockout mice show evidence of ethanol self-administration, and, in fact, these mice showed evidence of an aversion to ethanol under several experimental conditions. These data provide new evidence for a critical role for μ-opioid receptors in ethanol self-administration assessed with a variety of behavioral paradigms and new insights into the neuropharmacological basis for ethanol reinforcement.

Footnotes

  • Send reprint requests to: Amanda J. Roberts, Ph.D., Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. E-mail:aroberts{at}scripps.edu

  • ↵1 This study was supported by National Institutes of Health Grant AA 06420 from the National Institute on Alcohol Abuse and Alcoholism and by the Mission Interministerielle de Lutte contre la Drogue et la Toxicomanie.

  • ↵2 This is publication number 12358-NP from The Scripps Research Institute.

  • ↵3 Current address: Department of Psychology, Franklin and Marshall College, P.O. Box 3003, Lancaster, PA 17604-3003.

  • ↵4 Current address: Centre National de la Recherche Scientifique UPR 9050, ESBS Parc d'innovation Bld s., Brandt, 67400 Illkirch, France.

  • Abbreviations:
    WT
    wild-type
    KO
    knockout
    FR
    fixed ratio
    • Received December 3, 1999.
    • Accepted January 25, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 293 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 3
1 Jun 2000
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Research ArticleNEUROPHARMACOLOGY

μ-Opioid Receptor Knockout Mice Do Not Self-Administer Alcohol ,

Amanda J. Roberts, Jeffrey S. McDonald, Charles J. Heyser, Brigitte L. Kieffer, Hans W. D. Matthes, George F. Koob and Lisa H. Gold
Journal of Pharmacology and Experimental Therapeutics June 1, 2000, 293 (3) 1002-1008;

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Research ArticleNEUROPHARMACOLOGY

μ-Opioid Receptor Knockout Mice Do Not Self-Administer Alcohol ,

Amanda J. Roberts, Jeffrey S. McDonald, Charles J. Heyser, Brigitte L. Kieffer, Hans W. D. Matthes, George F. Koob and Lisa H. Gold
Journal of Pharmacology and Experimental Therapeutics June 1, 2000, 293 (3) 1002-1008;
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