2003-04002-017 - 17 G enetic and E nvironmental Risks of D...

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17 Genetic and Environmental Risks of Dependence on Alcohol, Tobacco, Other Drugs Andrew C. Heath, Pamela A. l? Madden, Kathleen K. Bucholz, Elliot C. Nelson, Alexandre Todorov, Rumi Kato Price, John B. Whitfield, and Nicholas G. Martin The field of genetic research on addiction vulnerability, defined here as research designed to understand individual differences in risk of depen- dence on, or persistent harmhl use of, alcohol, tobacco, or illicit drugs, offers great opportunities but also considerable challenges. Because genes have been identified that influence the metabolism of alcohol and have effects on alcohol-dependence risk (ALDH2, ADH2) or that influence the metabolism of nicotine (CyP2A6), the addiction field already provides il- lustration of the complexities that are to be anticipated as we identify other individual gene effects on human behavior. As reviewed elsewhere (see Crabbe, chapter 16, this volume), the ability to study drug effects in mice, rats, and other experimental organisms makes possible controlled breeding experiments that ultimately may identify the involvement of pre- viously unsuspected genes in the regulation of responses to individual licit or illicit drugs, and also makes possible the dissection of the central ner- vous system effects of these drugs in ways that would not be possible in humans. Controlled dosing of humans, in drug challenge studies con- ducted in the human experimental laboratory, offers the possibility of iden- tifying aspects of drug response (e.g., postalcohol “ataxia,” or body sway; subjective, cardiovascular, and other physiological reactions to alcohol, nic- otine, or other drugs) that are under simpler genetic control than more complex constructs such as dependence. At the same time, the challenges of understanding the complex interplay of genetic and environmental in- fluences on behavior are particularly great for human drug use and de- pendence, where environmental influences may begin prenatally (through fetal alcohol effects; Streissguth et al., 1994; Yates, Cadoret, Troughton, This work was supported by National Institutes of Health Grants AA07728, AA11224, AA11998, AA13321, CA75581, and DMCA12854. 309
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