The μ-opioid receptor, OPRM1, has been investigated for a role in the subjective response to acute amphetamine. Stimulation of μ-opioid receptors by endogenous beta-endorphins in the ventral tegmental area increases dopamine release (Spanagel et al. 1992); therefore, variation in OPRM1 may influence dopamine release and therefore response to stimulants. A commonly studied coding polymorphism within OPRM1, Asp40Asn (A118G; rs1799971; A/G), was first described by Bergen et al. (1997) and has been associated with numerous phenotypes, including heroin addiction (Drakenberg et al. 2006), schizophrenia (Šerý et al. 2010), and naltrexone treatment response (Oroszi et al. 2009). This SNP has also been shown to alter binding of beta-endorphin to the receptor (Bond et al. 1998). We examined associations between several SNPs (including rs1799971) and the acute responses to amphetamine on the ARCI Euphoria, Energy and Stimulation scales (Dlugos et al. 2010), and found that two polymorphisms (rs510769 G/G, A/G and rs2281617 C/C) were associated with increased euphoric responses to amphetamine at 10 mg; rs510769 is in strong linkage disequilibrium with rs1799971. The results indicate that variation in OPRM1 may be related to variation in positive, euphoric responses to amphetamine.
