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Ethanol consumption and resistance are inversely related to neuropeptide Y levels

Nature volume 396, pages 366–369 (1998)Cite this article

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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Figure 1: Consumption of ethanol and recovery from ethanol-induced sedation by NPY−/− and wild-type (129/sv × C57BL/6; NPY+/+) mice.
Figure 2: Generation and biochemical characterization of transgenic mice that overexpress a marked NPY gene.
Figure 3: Ethanol consumption and recovery from ethanol-induced sedation by NPY-overexpressing mice (NPY-OX) and wild-type littermates (FVB; NPY+/+).

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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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Authors and Affiliations

  1. Department of Psychology, University of Washington, Box 351525, Seattle, 98195, Washington, USA

    Todd E. Thiele & Ilene L. Bernstein

  2. Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Box 357370, Seattle, 98195, Washington, USA

    Donald J. Marsh, Linda Ste. Marie & Richard D. Palmiter

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  1. Todd E. Thiele
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Correspondence to Todd E. Thiele.

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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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