Ethanol consumption and reward are decreased in mu-opiate receptor knockout mice.
BACKGROUND
Differences in mu-opiate receptor (MOR) gene expression may modulate the rewarding effects of ethanol.


OBJECTIVE
The effects of MOR gene knockout (KO) were examined in wild-type (+/+), heterozygote MOR KO (+/-), and homozygote MOR KO (-/-) mice on voluntary ethanol consumption, conditioned place preference produced by ethanol, and locomotor responses to ethanol in separate groups of mice.


METHODS
Voluntary ethanol consumption (2-32% v/v) was examined in a two-bottle home-cage consumption test. The conditioned place preference paradigm was a biased design. Mice received four pairings of ethanol (2.0 g/kg IP) on the initially preferred side and four pairings on the initially non-preferred side with saline. The difference in time spent on the initially non-preferred side (pre- versus post-conditioning) was the measure of drug-induced preference. After habituation to a novel locomotor test chamber mice were tested, on subsequent sessions, for ethanol induced locomotion (0.0, 0.5, 1.0, and 2.0 g/kg IP).


RESULTS
Heterozygous and homozygous MOR KO mice consumed less ethanol than wild-type mice. These effects appeared to be greater in female KO mice than in male KO mice. MOR KO mice, especially females, exhibited less ethanol reward in a conditioned place preference paradigm. These effects on ethanol reward were produced by reductions in MOR expression levels as small as 50%. MOR KO mice exhibited less ethanol-stimulated locomotion than did wild-type mice, an effect that was also largest in females.


CONCLUSIONS
These data fit with the reported therapeutic efficacy of MOR antagonists in the treatment of human alcoholism. Allelic variants that confer differing levels of MOR expression could provide different degrees of risk for alcoholism.
Hall
F S
FS
Molecular Neurobiology Branch, Intramural Researcch Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Shall@intra.nida.nih.gov
Sora
I
I
Uhl
G R
GR
D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000502:physiology*; D012201:Reward
D017450:Receptors, Opioid, mu