brain regions can then be identified, and these regions can be targeted for molecular and cellular analyses to understand the underlying mechanisms involved. Understanding the role of these brain structures in drug dependence will provide key information linking the well-studied mesolimbic system to other limbic structures implicated in emotions and motivated behavior and will provide a rich substrate for understanding etiology, vulnerability, and relapse.

RESEARCH OPPORTUNITIES

Genetics Research

A major goal of future research is to identify genes that contribute to individual vulnerability to drug addiction. The identification of drug addiction vulnerability genes, like the identification of any disease vulnerability gene, will require careful and thorough policy analysis and implementation. Although most research in this area has involved genetic studies in people, the focus has been on candidate genes for which there is little preclinical evidence for a role in vulnerability to dependence. For example, much of the effort in the field has focused on alleles of monoamine receptors or transporters as candidate genes. Yet, there is little if any evidence in animals or people that individual differences in the functioning of those proteins contribute to individual differences in drug responsiveness.

A promising strategy, however, which has not been employed sufficiently to date, is the use of animal models for genetic studies. This strategy is analogous to that used with success in other medical specialties. Mapping of the mouse genome, and more recently the rat genome, is proceeding at a rapid pace. By use of a variety of experimental strategies such as quantitative trait locus analysis (Belknap et al., 1993), it is now feasible to begin the process of identifying genetic loci associated with specific behavioral phenotypes related to drug dependence. It is likely that genes identified through this process will include those that encode for proteins not currently thought of as being involved in drug dependence. Identification of drug dependence vulnerability genes in animals may reveal the types of genes involved in people. Even if the same homologous genes are not involved in people, genes that encode proteins along the same biochemical pathways would be additional candidate genes for investigation. This approach would involve the targeting of far more sophisticated candidate genes for analysis, rather than a continuation of the current approach. Thus, studies of inbred rodent strains could be used to identify genes leading to different preferences for initiating or chronically maintaining self-administration of commonly abused drugs.



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