Galanin Knockout Mice Show Disturbances in Ethanol Consumption and Expression of Hypothalamic Peptides That Stimulate Ethanol Intake

Authors

  • Olga Karatayev,

    1. From the Laboratory of Behavioral Neurobiology, Rockefeller University (OK, JB, VW, SC, SFL), New York, New York; and Departments of Pharmacology and Clinical Sciences, University of Bristol (DW), Bristol, U.K.
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  • Jessica Baylan,

    1. From the Laboratory of Behavioral Neurobiology, Rockefeller University (OK, JB, VW, SC, SFL), New York, New York; and Departments of Pharmacology and Clinical Sciences, University of Bristol (DW), Bristol, U.K.
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  • Valerie Weed,

    1. From the Laboratory of Behavioral Neurobiology, Rockefeller University (OK, JB, VW, SC, SFL), New York, New York; and Departments of Pharmacology and Clinical Sciences, University of Bristol (DW), Bristol, U.K.
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  • Siyi Chang,

    1. From the Laboratory of Behavioral Neurobiology, Rockefeller University (OK, JB, VW, SC, SFL), New York, New York; and Departments of Pharmacology and Clinical Sciences, University of Bristol (DW), Bristol, U.K.
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  • David Wynick,

    1. From the Laboratory of Behavioral Neurobiology, Rockefeller University (OK, JB, VW, SC, SFL), New York, New York; and Departments of Pharmacology and Clinical Sciences, University of Bristol (DW), Bristol, U.K.
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  • Sarah F. Leibowitz

    1. From the Laboratory of Behavioral Neurobiology, Rockefeller University (OK, JB, VW, SC, SFL), New York, New York; and Departments of Pharmacology and Clinical Sciences, University of Bristol (DW), Bristol, U.K.
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Reprints requests: Dr. Sarah F. Leibowitz, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Fax: 212-327-8447; E-mail: leibow@rockefeller.edu

Abstract

Background:  There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat-rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice.

Methods:  Two groups of female and male GALKO mice, compared to wild-type (WT) controls, were trained to voluntarily drink increasing concentrations of ethanol, while maintained on lab chow and water. They were examined in terms of their daily ethanol intake and preference, acute consumption of a high-fat diet, preference for flavored solutions, and expression of different peptides shown to stimulate ethanol intake.

Results:  In the GALKO mice compared to WT, the results revealed: (i) a 35 to 45% decrease in ethanol intake and preference, which was evident only at the highest (15%) ethanol concentration, was stronger in female than in male mice, and was seen with comparisons to littermate as well as nonlittermate WT mice; (ii) a 48% decrease in acute intake of a fat-rich diet, again stronger in female than male mice; (iii) no difference in consumption of sucrose or quinine solutions in preference tests; (iv) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus (PVN) of female and male mice; and (v) a gender-specific change in mRNA levels of peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin-concentrating hormone, which are known to stimulate ethanol and food intake and were markedly decreased in females while increased in males.

Conclusions:  These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat-rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males.

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