Genetics of alcohol and other abused drugs

Abstract

Genetic approaches have been applied to the study of all drugs of abuse with varying degrees of ardor. Systematic ‘modern’ studies of the genetic influence on drug sensitivity date at least to the late 1940s, Ž . when Mardones 1951 demonstrated that rats could be genetically selected for high or low alcohol drinking. This basic experiment has been repeated many times over, with increasing sophistication. A Ž . systematic and nearly but not completely successful attempt to review all published studies of genetic contributions to individual differences in response to alcohol, barbiturates, opiates, benzodiazepines, cocaine, amphetamine, nicotine and other drugs through Ž early 1991 has been published Crabbe and Harris, . 1991 . Chapters in that volume and many subsequent Ž reviews e.g. Smolen and Marks, 1991; Marley et al., 1992; Crabbe and Li, 1995; Uhl et al., 1995; Mogil et . al., 1996; Crawley et al., 1997; Buck et al., 1998 provide basic information about the many genetic strategies that have been employed for each class of abused drugs, concentrating on the use of genetic animal models in preclinical studies. A useful introduction to the methods employed with human populations to establish genetic influence is provided by Ž . Crowe 1995 . This minireview will only briefly describe genetic methods and their strengths and weaknesses, and will concentrate on recent findings. The reader will be referred to relevant reviews for more details about specific approaches. Also, the review will focus on genetic influences on drug sensitivity and drug seeking not controlled by differences in bioavailability at the brain targets of abused drugs. While there are many human studies implicating genetic predisposi-