title: mu-Opioid receptor knockout mice do not self-administer alcohol.
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 mu-opioid receptor knockout mice has made possible the direct examination of the role of the mu-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 mu-opioid receptors in ethanol self-administration assessed with a variety of behavioral paradigms and new insights into the neuropharmacological basis for ethanol reinforcement.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. aroberts@scripps.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: J S
authors.initials: JS
authors.lastname: McDonald
authors.forename: C J
authors.initials: CJ
authors.lastname: Heyser
authors.forename: B L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: H W
authors.initials: HW
authors.lastname: Matthes
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
authors.forename: L H
authors.initials: LH
authors.lastname: Gold
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D003216:Conditioning, Operant; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D017450:Receptors, Opioid, mu