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.
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Acknowledgements
We thank E. Sandgren for generating the NPY-OX mouse lines; G. Hollopeter and R.Cherne for help on maintaining and genotyping mice; I. Cubero and M. Miller for help in collecting data; and R. J. Seeley, L. Carr and T.-K. Li for comments and suggestions. This work was supported in part by the NIH and the University of Washington Alcohol and Drug Abuse Institute.
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Thiele, T., Marsh, D., Ste. Marie, L. et al. Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396, 366–369 (1998). https://doi.org/10.1038/24614
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DOI: https://doi.org/10.1038/24614
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