Ethanol consumption and resistance are inversely related to neuropeptide Y levels.
Genetic linkage analysis of rats that were selectively bred for alcohol preference identified a chromosomal region that includes the neuropeptide Y (NPY) gene. Alcohol-preferring rats have lower levels of NPY in several brain regions compared with alcohol-non-preferring rats. We therefore studied alcohol consumption by mice that completely lack NPY as a result of targeted gene disruption. Here we report that NPY-deficient mice show increased consumption, compared with wild-type mice, of solutions containing 6%, 10% and 20% (v/v) ethanol. NPY-deficient mice are also less sensitive to the sedative/hypnotic effects of ethanol, as shown by more rapid recovery from ethanol-induced sleep, even though plasma ethanol concentrations do not differ significantly from those of controls. In contrast, transgenic mice that overexpress a marked NPY gene in neurons that usually express it have a lower preference for ethanol and are more sensitive to the sedative/hypnotic effects of this drug than controls. These data are direct evidence that alcohol consumption and resistance are inversely related to NPY levels in the brain.
Thiele
T E
TE
Department of Psychology, University of Washington, Seattle 98195, USA. thiele@u.washington.edu
Marsh
D J
DJ
Ste Marie
L
L
Bernstein
I L
IL
Palmiter
R D
RD
D000428:Alcohol Drinking; D000818:Animals; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000172:deficiency / Q000502:physiology*; D013649:Taste
D006993:Hypnotics and Sedatives; D009478:Neuropeptide Y; D000431:Ethanol