Naltrexone Modification of Drinking Effects in a Subacute Treatment and Bar-Lab Paradigm: Influence of OPRM1 and Dopamine Transporter (SLC6A3) Genes

Alcoholism: Clinical and Experimental Research, 05/07/2012

This study does not support a salient role for the opioid receptor (OPRM1) asp40 alone in predicting drinking or naltrexone effects. However, although exploratory and in need of replication, it introduces the possibility that epistasis between the OPRM1 gene and dopamine transporter gene might need to be taken into account when examining differential genetic response to alcohol or medication treatment, especially in early–stage alcoholics.

Methods

  • Two hundred and sixty-five nontreatment-seeking individuals with alcohol dependence were genotyped a priori for the OPRM1 asn40asp SNP and post hoc for DAT (SLC6A3) 9 and 10 VNTRs.
  • 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 OPRM1 genotype, or any medication by OPRM1 interaction, on drinking variables.
  • However, in individuals who had at least one DAT 9 VNTR, and who were also OPRM1 asn40 homozygotes, naltrexone reduced drinks/d consumed under natural conditions (p = 0.006), but not in the bar-lab.
  • OPRM1 asn40 homozygotes (p = 0.028) and DAT 9 VNTR carriers (p = 0.032) had more stimulation to alcohol after the priming drink.

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