| Acamprosate-responsive brain sites for suppression of ethanol intake and preference. | |
MedLine Citation:
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PMID: 21697518 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acamprosate suppresses alcohol intake and craving in recovering alcoholics; however, the central sites of its action are unclear. To approach this question, brain regions responsive to acamprosate were mapped using acamprosate microimplants targeted to brain reward and circadian areas implicated in alcohol dependence. mPer2 mutant mice with nonfunctional mPer2, a circadian clock gene that gates endogenous timekeeping, were included, owing to their high levels of ethanol intake and preference. Male wild-type (WT) and mPer2 mutant mice received free-choice (15%) ethanol/water for 3 wk. The ethanol was withdrawn for 3 wk and then reintroduced to facilitate relapse. Four days before ethanol reintroduction, mice received bilateral blank or acamprosate-containing microimplants releasing ∼50 ng/day into reward [ventral tegmental (VTA), peduculopontine tegmentum (PPT), and nucleus accumbens (NA)] and circadian [intergeniculate leaflet (IGL) and suprachiasmatic nucleus (SCN)] areas. The hippocampus was also targeted. Circadian locomotor activity was measured throughout. Ethanol intake and preference were greater in mPer2 mutants than in wild-type (WT) mice (27 g·kg(-1)·day(-1) vs. 13 g·kg(-1)·day(-1) and 70% vs. 50%, respectively; both, P < 0.05). In WTs, acamprosate in all areas, except hippocampus, suppressed ethanol intake and preference (by 40-60%) during ethanol reintroduction. In mPer2 mutants, acamprosate in the VTA, PPT, and SCN suppressed ethanol intake and preference by 20-30%. These data are evidence that acamprosate's suppression of ethanol intake and preference are manifest through actions within major reward and circadian sites. |
Authors:
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Allison Brager; Rebecca A Prosser; J David Glass |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-06-22 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 301 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-07 Completed Date: 2011-12-06 Revised Date: 2014-09-09 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R1032-43 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Deterrents
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pharmacology* Alcohol Drinking / physiopathology* Animals Brain / drug effects*, physiology* Circadian Rhythm / physiology Drinking / drug effects, physiology Food Preferences / drug effects*, physiology* Hippocampus / drug effects, physiology Male Mice Mice, Inbred C57BL Mice, Mutant Strains Models, Animal Motor Activity / drug effects, physiology Nucleus Accumbens / drug effects, physiology Pedunculopontine Tegmental Nucleus / drug effects, physiology Period Circadian Proteins / genetics, physiology Suprachiasmatic Nucleus / drug effects, physiology Taurine / analogs & derivatives*, pharmacology Ventral Tegmental Area / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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AA-015948/AA/NIAAA NIH HHS; AA-017898/AA/NIAAA NIH HHS; R01 AA017898/AA/NIAAA NIH HHS; R01 AA017898-03/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Alcohol Deterrents; 0/Per2 protein, mouse; 0/Period Circadian Proteins; 1EQV5MLY3D/Taurine; N4K14YGM3J/acamprosate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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