Pharmacogenetic strategies for studying alcohol dependence.

The importance of genotypic differences in the determination of sensitivity to ethanol, tolerance development and physical dependence susceptibility is achieving ever greater recognition. It is now generally accepted by investigators studying the biochemical and physiological bases for alcoholism that genotype can influence all these different aspects of sensitivity to the effects of ethanol. Although there is convincing evidence that susceptibility to alcoholism is inherited in man, we have no idea what it is that is inherited [2, 7, 19, 24, 31]. By examining a family history for a particular individual, we can identify individuals at familial risk for developing problems with alcohol abuse. However, environmental as well as genetic factors are important in determining who does and who does not become an alcoholic [4]. Thus, one critical need is for a genetic marker for alcoholism. Since the search for such markers in human research is both expensive and time-consuming, this has led to the use of animal models for alcoholism. Animal models are particularly helpful for genetic research since their genetics are well understood and can be specifically tooled to the task at hand. The goal of this paper is to illustrate the principal genetic methodologies that have been employed to study the human and animal pharmacogenetics of alcohol, and to identify future directions in this area.