The rewarding properties of nicotine are, in part, mediated by opioid transmission. For instance, it has been shown that nicotine stimulates the release of endogenous opioids in reward-related brain regions (Davenport et al., 1990; Pomerleau, 1998), blockade of MOPRs with systemic injections of naloxone blocks acute nicotine reward (Walters et al., 2005), MOPR null mutant mice do not show nicotine reward (Berrendero et al., 2002), and repeated treatment with nicotine elevates MOPR mRNA in the VTA (Walters et al., 2005). Human studies have reported an association of chromosome 6, which contains OPRM1, with nicotine dependence (Sullivan et al., 2004; Vink et al., 2004) (Table 1). Another study, however, found that the A118G SNP was not significantly associated with nicotine dependence, though it was in high linkage disequilibrium with haplotypes that did reach significance, suggesting there may be other SNPs nearby that confer an increased susceptibility for developing nicotine dependence (Zhang et al., 2006b). As in the case with alcohol, studies examining differences in response to nicotine administration have revealed some interesting associations. For instance, female G118 allele-carriers report attenuated rewarding
