Abstract
Recent history has seen a surge of interest in the phenomenon of drug sensitization (reverse tolerance), in part because sensitization has been suggested as an important factor in the development of drug abuse. Genetic variation plays a key role in sensitivity to many drug effects, as well as predilection toward alcohol and drug abuse. The goal of this review was to critically evaluate the literature investigating the behavioral genetics of drug sensitization. A moderate amount of animal work utilizing inbred strains, selected lines, and recombinant inbred strains has been done that unsurprisingly supports partial genetic control of sensitization. Genes determining quantitative variation in degree of sensitization to cocaine and ethanol have been provisionally mapped to specific chromosomal regions in the mouse. However, research toward establishing a link between sensitization and risk for drug abuse and toward identifying the genetic mediators of sensitization needs to be expanded. Information derived from congenic strains, transgenic mice, knockout and inducible knockout mice could lead to better medical intervention for drug addiction.
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