RT Journal Article SR Electronic T1 μ-Opioid Receptor Knockout Mice Do Not Self-Administer Alcohol , JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1002 OP 1008 VO 293 IS 3 A1 Amanda J. Roberts A1 Jeffrey S. McDonald A1 Charles J. Heyser A1 Brigitte L. Kieffer A1 Hans W. D. Matthes A1 George F. Koob A1 Lisa H. Gold YR 2000 UL http://jpet.aspetjournals.org/content/293/3/1002.abstract AB 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. The American Society for Pharmacology and Experimental Therapeutics