Ethanol consumption and resistance are inversely related to neuropeptide Y levels

Todd E. Thiele (), Donald J. Marsh, Linda Ste. Marie, Ilene L. Bernstein and Richard D. Palmiter
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Todd E. Thiele: University of Washington
Donald J. Marsh: University of Washington
Linda Ste. Marie: University of Washington
Ilene L. Bernstein: University of Washington
Richard D. Palmiter: University of Washington

Nature, 1998, vol. 396, issue 6709, 366-369

Abstract: Abstract Genetic linkage analysis of rats that were selectively bred for alcohol preference identified a chromosomal region that includes the neuropeptide Y (NPY) gene1. Alcohol-preferring rats have lower levels of NPY in several brain regions compared with alcohol-non-preferring rats2. We therefore studied alcohol consumption by mice that completely lack NPY as a result of targeted gene disruption3. 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.

Date: 1998
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DOI: 10.1038/24614

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