The μ-opioid receptor encoded by the OPRM1 gene is a key factor contributing to drug addiction [5]. The μ-opioid receptor is a major site of action for endogenous opioid peptides and exogenous opioid drugs. More interestingly, some non-opioid substances including nicotine that have other primary sites of action are likely to induce the release of endogenous opioid peptides, and subsequently activate the μ receptor [5]. For instance, experiments have shown that nicotine causes a release of endogenous opioids in the brains of rat and mouse [6]. Recent studies using inbred and knockout mice strongly suggest that the μ-opioid receptor mediates both the positive and negative reinforcing effects of nicotine. Nicotine-induced antinociception, reward effects and dependence are substantially attenuated in mice lacking the μ-opioid receptor [7,8]. This implies that some aspects of the rewarding valence of nicotine require μ opioid receptors. In humans, opioid receptor antagonist naloxone may reduce the relative reinforcing effects of nicotine, thus it has been used as a smoking cessation drug [9-11]. Lerman and colleagues show that a variant in OPRM1 may predict the treatment responses to
