Document Detail

Acamprosate-responsive brain sites for suppression of ethanol intake and preference.
MedLine Citation:
PMID:  21697518     Owner:  NLM     Status:  MEDLINE    
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 The ethanol was withdrawn for 3 wk and then reintroduced to facilitate relapse.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.
Allison Brager; Rebecca A Prosser; J David Glass
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-22
Journal Detail:
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:
Created Date:  2011-10-07     Completed Date:  2011-12-06     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1032-43     Citation Subset:  IM    
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MeSH Terms
Alcohol Deterrents / pharmacology*
Alcohol Drinking / physiopathology*
Brain / drug effects*,  physiology*
Circadian Rhythm / physiology
Drinking / drug effects,  physiology
Food Preferences / drug effects*,  physiology*
Hippocampus / drug effects,  physiology
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
Reg. No./Substance:
0/Alcohol Deterrents; 0/Per2 protein, mouse; 0/Period Circadian Proteins; 1EQV5MLY3D/Taurine; N4K14YGM3J/acamprosate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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