Association of OPRM1 A118G variant with the relative reinforcing value of nicotine

Abstract

This study provides initial evidence for an association of the OPRM1 A118G variant with nicotine reinforcement in women.

Human Mu Opioid Receptor ( OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers

“…These regions have high MOR density (19)(20)(21) and are important in the mesolimbic reward circuits in addiction (22). Thus, the current findings may partly explain the reduced nicotine reward, withdrawal, and relapse risk associated with the A118G polymorphism (12)(13)(14)25).…”

“…Further, the current study was designed to eliminate carryover effects of smoking by scanning smokers on two separate occasions. It will be important in future studies to include sufficient numbers of males and females, as the behavioral effects of this polymorphism may be sex specific (14,18,35), and female sex and estradiol alter MOR binding availability (36,37).…”

“…A common single nucleotide polymorphism (SNP) in the mu-opioid receptor gene (OPRM1 A118G) results in an amino acid exchange at a putative glycosylation site in the extracellular terminus of the MOR (10). This OPRM1 SNP has been associated with a variety of drug dependence phenotypes in rodent and human studies (11), including nicotine reward, nicotine withdrawal severity, and smoking relapse (12)(13)(14).Despite substantial attention to the OPRM1 A118G in drug addiction research, the precise function of this SNP has yet to be clarified. Although the minor (G) allele was originally thought to be a "gain-of-function" variant, on the basis of increased affinity of MOR agonists (15), other data suggest that the G allele is associated with reduced mRNA and protein expression (16,17).…”

“…A common single nucleotide polymorphism (SNP) in the mu-opioid receptor gene (OPRM1 A118G) results in an amino acid exchange at a putative glycosylation site in the extracellular terminus of the MOR (10). This OPRM1 SNP has been associated with a variety of drug dependence phenotypes in rodent and human studies (11), including nicotine reward, nicotine withdrawal severity, and smoking relapse (12)(13)(14).…”

“…On the basis of the finding of reduced protein levels of MOR in knock-in mice that carry the G allele (18), we predicted that OPRM1 G allele carriers would have reduced MOR BP ND compared with those homozygous for the A allele. Furthermore, we hypothesized that the extent of displacement of the radioligand (i.e., changes in MOR BP ND across the two sessions) would be reduced in smokers with the G allele (14). Regions with high MOR density (19)(20)(21), which are important in the mesolimbic reward circuits in addiction (22), were selected as regions of interest (ROIs): anterior cingulate cortex (ACC), amygdala (AMY), caudate (CAU), ventral striatum/nucleus accumbens (VST), and thalamus (THA).…”