mu-Opioid receptor knockout mice do not self-administer alcohol.
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.
Roberts
A J
AJ
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. aroberts@scripps.edu
McDonald
J S
JS
Heyser
C J
CJ
Kieffer
B L
BL
Matthes
H W
HW
Koob
G F
GF
Gold
L H
LH
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
D017450:Receptors, Opioid, mu