potential: preliminary findings in human subjects

The Asn40Asp variant (A118G) of the m opioid receptor (OPRM1) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies binding potential (BPND )o f the m-selective ligand ( 11 C)carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BPND at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9 %) compared to AA subjects (93.1 %), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.