Document Detail


Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues.
MedLine Citation:
PMID:  23032071     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Variation at a single nucleotide polymorphism in the μ-opioid receptor gene (OPRM1), A118G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and A118G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and A118G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT1/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and A118G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the A118G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or A118G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT1 variation also moderated medication/A118G effects. There was a three-way interaction between medication and A118G and DAT1 genotypes on VS activation, such that, among G-allele carriers who received NTX, DAT1 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, 10R homozygotes who received NTX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM1 and DAT1 should be considered in future studies of NTX, particularly regarding its effects on reward processing.
Authors:
Joseph P Schacht; Raymond F Anton; Konstantin E Voronin; Patrick K Randall; Xingbao Li; Scott Henderson; Hugh Myrick
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2012-10-03
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  38     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-10-17     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  414-22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Alcohol Drinking / genetics,  metabolism
Alcoholism / drug therapy,  genetics*,  metabolism
Cues*
Dopamine Plasma Membrane Transport Proteins / genetics*
Female
Genetic Variation / genetics*
Humans
Magnetic Resonance Imaging / methods
Male
Naltrexone / pharmacology,  therapeutic use*
Narcotic Antagonists / pharmacology,  therapeutic use
Polymorphism, Genetic
Polymorphism, Single Nucleotide / genetics
Protein Binding / physiology
Receptors, Opioid, mu / antagonists & inhibitors,  genetics*
Tandem Repeat Sequences / genetics
Treatment Outcome
Young Adult
Grant Support
ID/Acronym/Agency:
K05 AA017435/AA/NIAAA NIH HHS; K05 AA017435/AA/NIAAA NIH HHS; P50 AA010761/AA/NIAAA NIH HHS; P50 AA010761/AA/NIAAA NIH HHS; T32 AA007474/AA/NIAAA NIH HHS; T32 AA007474/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Plasma Membrane Transport Proteins; 0/Narcotic Antagonists; 0/OPRM1 protein, human; 0/Receptors, Opioid, mu; 0/SLC6A3 protein, human; 5S6W795CQM/Naltrexone
Comments/Corrections

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


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