Heroin directly stimulates MOPRs when converted to morphine in the brain and periphery. Similarly to alcohol, this results in activation of reward-related pathways, initially resulting in euphoria, but eventually leading to abuse and dependence. Studies evaluating the role of G118 allele in heroin dependence have reported positive associations (Bart et al., 2004; Drakenberg et al., 2006; Kapur et al., 2007; Szeto et al., 2001), negative associations (Bond et al., 1998; Tan et al., 2003), or no association (Glatt et al., 2007; Shi et al., 2002) (Table 1). For instance, one study found that approximately 90% of G118 allele-carriers were heroin users. Additionally, they found that preproenkephalin and preprodynorphin levels, which were reduced in heroin-dependent subjects, were even lower in G118 allele-carriers compared with A118 allele-carriers (Drakenberg et al., 2006). Shi and colleagues found that the G118 allele was associated with elevated daily intake of heroin in dependent subjects, though they did not find a significant effect of genotype and heroin dependence (Shi et al., 2002). A positive response to initial drug exposure is typically associated with continued use and abuse.
