Genetic analysis offers a hypothesis-free approach that could be used to discover the mechanisms mediating maladaptive responses to opiates, and this information could lead to novel therapeutic strategies. Inter-individual genetic differences among human populations have been shown to explain a substantial fraction of the variance in clinically relevant responses to opioids [6, 7]. We expect genetic approaches in mice to also be informative, since there are very large differences in the response of inbred strains to opiates, including the development of opioid analgesia, tolerance, dependence and hyperalgesia [8–14]. In fact, HBCGM, which used SNP databases generated from limited sequence information, has identified several involved genes including those coding for β2-adrenergic and 5-HT3 receptors that affect opiate responses, and these findings were translated to humans [8, 15].
