Substance abuse is a multi-factorial illness that results from both genetic and environmental risk factors. The genetic risk for substance abuse is likely determined by different neurobiological and genetic vulnerabilities that may be specific to different stages of the disease. Clinical diagnoses such as those in the DSM IV have been defined by the medical community for purposes of diagnosis and treatment. These diagnoses were not designed to facilitate genetic studies and may not correspond to discrete biological phenomena. In this article, we divide substance abuse into six stages (Table 1) which may be influenced by separate, but overlapping genetic factors. Thus, we hypothesize that alleles that are associated with a diagnoses of substance abuse are mediated via their effects on one or more of these stages. This is especially important for translating to animal models because there are behavioral paradigms that attempt to model each of these stages. Therefore, animal models might be used to understand at what stage a particular gene or allele influences the progression toward substance abuse.
