| Alteration of ethanol drinking in mice via modulation of the GABA(A) receptor with ganaxolone, finasteride, and gaboxadol. | |
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MedLine Citation:
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PMID: 21649668 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Neurosteroids and other γ-aminobutyric acid(A) (GABA(A) ) receptor-modulating compounds have been shown to affect ethanol intake, although their mechanism remains unclear. This study examined how patterns of 24-hour ethanol drinking in mice were altered with the synthetic GABAergic neurosteroid ganaxolone (GAN), with an inhibitor of neurosteroid synthesis (finasteride [FIN]), or a GABA(A) receptor agonist with some selectivity at extrasynaptic receptors (gaboxadol HCL [THIP]). METHODS: Male C57BL/6J mice had continuous access to a 10% v/v ethanol solution (10E) or water. Using lickometer chambers, drinking patterns were analyzed among mice treated in succession to GAN (0, 5, and 10 mg/kg), FIN (0 or 100 mg/kg), and THIP (0, 2, 4, 8, and 16 mg/kg). RESULTS: GAN shifted drinking in a similar but extended manner to previous reports using low doses of the neurosteroid allopregnanolone (ALLO); drinking was increased in hour 1, decreased in hours 2 and 3, and increased in hours 4 and 5 postinjection. THIP (8 mg/kg) and FIN both decreased 10E drinking during the first 5 hours postinjection by 30 and 53%, respectively, while having no effect on or increasing water drinking, respectively. All 3 drugs altered the initiation of drinking sessions in a dose-dependent fashion. FIN increased and GAN decreased time to first lick and first bout. THIP (8 mg/kg) decreased time to first lick but increased time to first bout and attenuated first bout size. CONCLUSIONS: The present findings support a role for the modulation of ethanol intake by neurosteroids and GABA(A) receptor-acting compounds and provide hints as to how drinking patterns are shifted. The ability of THIP to alter 10E drinking suggests that extrasynaptic GABA(A) receptors may be involved in the modulation of ethanol intake. Further, the consistent results with THIP to that seen previously with high doses of ALLO suggest that future studies should further examine the relationship between neurosteroids and extrasynaptic GABA(A) receptors, which could provide a better understanding of the mechanism by which neurosteroids influence ethanol intake. |
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Authors:
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Marcia J Ramaker; Matthew M Ford; Andrea M Fretwell; Deborah A Finn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-06-07 |
Journal Detail:
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Title: Alcoholism, clinical and experimental research Volume: 35 ISSN: 1530-0277 ISO Abbreviation: Alcohol. Clin. Exp. Res. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-02 Completed Date: 2012-03-26 Revised Date: 2013-02-19 |
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: 1994-2007 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 by the Research Society on Alcoholism. |
Affiliation:
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Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. ramakerm@ohsu.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Drinking
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physiopathology* Animals Behavior, Animal / drug effects, physiology Dose-Response Relationship, Drug Drinking Behavior / drug effects*, physiology Finasteride / pharmacology* GABA-A Receptor Agonists / pharmacology Isoxazoles / pharmacology* Male Mice Mice, Inbred C57BL Models, Animal Pregnanolone / analogs & derivatives*, pharmacology Receptors, GABA-A / drug effects*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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K01 AA016849-01/AA/NIAAA NIH HHS; KO1 AA16849/AA/NIAAA NIH HHS; R01 AA012439-08/AA/NIAAA NIH HHS; R01 AA016981/AA/NIAAA NIH HHS; R01 AA016981-02/AA/NIAAA NIH HHS; R01 AA016981-04/AA/NIAAA NIH HHS; R01 AA12439/AA/NIAAA NIH HHS; R01 AA16981/AA/NIAAA NIH HHS; T32 AA007468/AA/NIAAA NIH HHS; T32 AA007468-21/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GABA-A Receptor Agonists; 0/Isoxazoles; 0/Receptors, GABA-A; 128-20-1/Pregnanolone; 38398-32-2/ganaxolone; 98319-26-7/Finasteride; K1M5RVL18S/gaboxadol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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