Document Detail


Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.
MedLine Citation:
PMID:  23389755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism.
OBJECTIVES: This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy.
METHODS: Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task.
RESULTS: There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking.
CONCLUSIONS: These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
Authors:
Joseph P Schacht; Raymond F Anton; Patrick K Randall; Xingbao Li; Scott Henderson; Hugh Myrick
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-07
Journal Detail:
Title:  Psychopharmacology     Volume:  227     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-24     Completed Date:  2013-12-18     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  627-37     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Alcohol Drinking / prevention & control
Alcoholism / rehabilitation*
Amines / administration & dosage,  therapeutic use*
Brain / drug effects,  metabolism
Cues
Cyclohexanecarboxylic Acids / administration & dosage,  therapeutic use*
Drug Therapy, Combination
Excitatory Amino Acid Antagonists / administration & dosage,  therapeutic use
Female
Flumazenil / administration & dosage,  therapeutic use*
Follow-Up Studies
GABA Modulators / administration & dosage,  therapeutic use
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Recurrence / prevention & control
Severity of Illness Index
Substance Withdrawal Syndrome / drug therapy*,  physiopathology
Treatment Outcome
gamma-Aminobutyric Acid / administration & dosage,  therapeutic use*
Grant Support
ID/Acronym/Agency:
K05 AA017435/AA/NIAAA NIH HHS; K05 AA017435/AA/NIAAA NIH HHS; T32 AA007474/AA/NIAAA NIH HHS; T32 AA007474/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Amines; 0/Cyclohexanecarboxylic Acids; 0/Excitatory Amino Acid Antagonists; 0/GABA Modulators; 40P7XK9392/Flumazenil; 56-12-2/gamma-Aminobutyric Acid; 6CW7F3G59X/gabapentin
Comments/Corrections

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


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