Reduced alcohol consumption in mice lacking preprodynorphin.
Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).
Blednov
Yuri A
YA
University of Texas, Waggoner Center for Alcohol and Addiction Research, 1 University Station A4800, Austin, TX 78712-0159, USA. yablednov@mail.utexas.edu
Walker
Danielle
D
Martinez
Marni
M
Harris
R Adron
RA
D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004399:Dynorphins / Q000235:genetics* / Q000502:physiology*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D004856:Postural Balance / Q000187:drug effects; D011498:Protein Precursors / Q000235:genetics* / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D012201:Reward; D012439:Saccharin / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013395:Sucrose / Q000494:pharmacology; D013649:Taste / Q000187:drug effects
D002492:Central Nervous System Depressants; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; C036448:pre-prodynorphin; D000431:Ethanol; D013395:Sucrose; D004399:Dynorphins; D012439:Saccharin