Neuropeptide Y Levels in Ethanol-Naive Alcohol-Preferring and Nonpreferring Rats and in Wistar Rats after Ethanol Exposure

Authors

  • Cindy L. Ehlers,

    Corresponding author
    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
      Reprint requests: Cindy L. Ehlers. Ph.D., Department of Neuropharmacology, The Scripps Research Institute, 10666 North Totrey Pines Road, CVN-14 La Jolla. CA 92037.
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  • Ting-Kai Li,

    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
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  • Lawrence Lurneng,

    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
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  • Bang H. Hwang,

    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
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  • Christine Somes,

    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
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  • Patricia Jimenez,

    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
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  • Aleksander A. Mathé

    1. Department of Neuropharmacology (C.L.E., C.S.). The Scripps Research Institute, La Jolla. California; Indiana University (T.-K.L., L.L., B.H.H.), School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana; and Department of Clinical Neuroscience (P.J., A.A.M.), Karolinska Institute. Stockholm. Sweden.
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  • This study was supported by the National Institute of Alcohol Abuse and Alcoholism Grants AA 00223 and AA 06059 to C.L.E., Grant AA 07611 to T-K. Li, and by a grant from the Karolinska Institute and the Swedish Medical Research Council 10414 to A.A.M. This research was presented in part at the 1997 ACNP meeting.

Reprint requests: Cindy L. Ehlers. Ph.D., Department of Neuropharmacology, The Scripps Research Institute, 10666 North Totrey Pines Road, CVN-14 La Jolla. CA 92037.

Abstract

Neuropeptide Y (NPY) is a hexatriacontapeptide amide that is now well characterized as a neuromodulator in the central nervous system (CNS). When infused into the CNS, NPY produces both anxiolytic and orexigenic effects. NPY's anxiolytic effects appear to be mediated through receptors in the central amygdala, whereas its orexigenic effects are localized in discrete hypothalamic nuclei. Both food restriction and food deprivation produce increased levels of the pep-tide in the hypothalamus that are ameliorated by refeeding. However, the effects of alcohol consumption/deprivation on NPY levels remain unknown. The present study sought to determine if brain NPY levels were affected by either alcohol exposure and/or correlated with genetic differences in preference for drinking alcohol. In the first experiment, NPY-like immunoreactivity (NPY-LI) was compared in alcohol-naive, alcohol-preferring (P), and nonpreferring (NP) rats. After tissue extraction, NPY-LI was measured by radioimmunoassay: amygdala, hippocampus, frontal cortex, hypothalamus, and caudate. P rats were found to have significantly lower NPY-LI in amygdala (F= 4.69, p 0.04), hippocampus (F= 7.03, p < 0.01), and frontal cortex (F= 4.7, p < 0.04), compared with NP rats. In the second experiment, heterozygous Wistar rats were exposed to alcohol for 14 hr/day for 7 weeks in alcohol vapor chambers (mean blood alcohol concentrations =180 mg%) or control chambers. At 7 weeks of alcohol exposure, no significant changes in NPY-LI in were found. At 1 month after ethanol withdrawal, however, the ethanol-exposed animals had significantly higher NPY-LI in the hypothalamus (F= 4.78, p < 0.04) when compared with the nonexposed controls. Taken together, these studies suggest that exposure to chronic ethanol may affect NPY-LI at the level of the hypothalamus in a fashion similar to food restriction, because 4 weeks after alcohol withdrawal, significantly higher NPY levels are found. In addition, differences in NPY-LI in limbic areas and frontal cortex between alcohol-naive P and NP rats suggest that NPY may also play a role in risk for the development of alcohol preference either by modulating the “tension-reduction” properties of alcohol or by influencing consummatory behaviors.

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