| Galanin knockout mice show disturbances in ethanol consumption and expression of hypothalamic peptides that stimulate ethanol intake. | |
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MedLine Citation:
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PMID: 19860804 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Olga Karatayev; Jessica Baylan; Valerie Weed; Siyi Chang; David Wynick; Sarah F Leibowitz |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2009-10-23 |
Journal Detail:
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Title: Alcoholism, clinical and experimental research Volume: 34 ISSN: 1530-0277 ISO Abbreviation: Alcohol. Clin. Exp. Res. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-18 Completed Date: 2010-08-10 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 7707242 Medline TA: Alcohol Clin Exp Res Country: England |
Other Details:
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Languages: eng Pagination: 72-80 Citation Subset: IM |
Affiliation:
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Laboratory of Behavioral Neurobiology, Rockefeller University, New York, New York, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Drinking
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genetics,
metabolism* Animals Ethanol / administration & dosage* Female Galanin / deficiency*, genetics Gene Expression Regulation* / drug effects Hypothalamic Hormones / biosynthesis*, genetics, physiology Hypothalamus / chemistry, metabolism*, physiology Intracellular Signaling Peptides and Proteins Male Mice Mice, Knockout Neuropeptides / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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AA 12882/AA/NIAAA NIH HHS; DA 21518/DA/NIDA NIH HHS; R01 DA021518-16A1/DA/NIDA NIH HHS; R01 DA021518-17/DA/NIDA NIH HHS; R01 DA021518-18/DA/NIDA NIH HHS; R01 DA021518-19/DA/NIDA NIH HHS; R01 MH043422-10/MH/NIMH NIH HHS; R01 MH043422-10S1/MH/NIMH NIH HHS; R01 MH043422-11A3/MH/NIMH NIH HHS; R01 MH043422-12/MH/NIMH NIH HHS; R01 MH043422-13/MH/NIMH NIH HHS; R01 MH043422-14/MH/NIMH NIH HHS; R01 MH043422-15/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hypothalamic Hormones; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/orexins; 64-17-5/Ethanol; 88813-36-9/Galanin |
| Comments/Corrections | |
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