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Naltrexone Modification of Drinking Effects in a Subacute Treatment and Bar‐Lab Paradigm: Influence of OPRM 1 and Dopamine Transporter ( SLC6A3 ) Genes
Author(s) -
Anton Raymond F.,
Voronin Konstantin K.,
Randall Patrick K.,
Myrick Hugh,
Tiffany Abraham
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01807.x
Subject(s) - naltrexone , opioid antagonist , placebo , craving , pharmacology , alcohol dependence , opioid , psychology , medicine , alcohol , biology , psychiatry , addiction , (+) naloxone , biochemistry , receptor , alternative medicine , pathology
Background Naltrexone is moderately effective for the treatment of alcohol dependence, but there is great individual variability. The opioid receptor ( OPRM 1 ) single nucleotide polymorphism ( SNP ) asn40asp has been shown to alter alcohol and naltrexone response in animals and humans. In addition, the brain opioid and dopamine systems interact and might underlie drinking and craving. This study investigated the effects of the OPRM 1 SNP and dopamine transporter ( DAT ) variable number of tandem repeat ( VNTR ) genetic differences on drinking, alcohol effects, and naltrexone response under controlled conditions in nontreatment‐seeking alcoholics. Methods Two hundred and sixty‐five nontreatment‐seeking individuals with alcohol dependence were genotyped a priori for the OPRM 1 asn40asp SNP and post hoc for DAT ( SLC 6A3 ) 9 and 10 VNTR s. Asp40 carriers ( n = 43) and matched asn40 homozygotes ( n = 40) were randomized to naltrexone or placebo for 7 days before receiving a priming drink and limited‐access alcohol consumption in a bar‐lab setting. Effects of genotypes on natural drinking as well as drinking, alcohol effects, and response to naltrexone in the bar‐lab setting were examined by genotype. Results There were no significant main effects of naltrexone or OPRM 1 genotype, or any medication by OPRM 1 interaction, on drinking variables. However, in individuals who had at least one DAT 9 VNTR , and who were also OPRM 1 asn40 homozygotes, naltrexone reduced drinks/d consumed under natural conditions ( p = 0.006), but not in the bar‐lab. OPRM 1 asn40 homozygotes ( p = 0.028) and DAT 9 VNTR carriers ( p = 0.032) had more stimulation to alcohol after the priming drink. Conclusions This study does not support a salient role for the OPRM 1 asp40 alone in predicting drinking or naltrexone effects. However, although exploratory and in need of replication, it introduces the possibility that epistasis between the OPRM 1 gene and DAT gene might need to be taken into account when examining differential genetic response to alcohol or medication treatment, especially in early‐stage alcoholics.