Ethanol consumption and resistance are inversely related to neuropeptide Y levels

Nature. 1998 Nov 26;396(6709):366-9. doi: 10.1038/24614.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Drinking*
  • Animals
  • Ethanol* / blood
  • Ethanol* / pharmacology
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuropeptide Y / deficiency
  • Neuropeptide Y / physiology*
  • Taste


  • Hypnotics and Sedatives
  • Neuropeptide Y
  • Ethanol