Many transgenic mouse models were made specifically made to investigate, under more controlled circumstances, the consequence of direct manipulation of particular genes, and for studying the roles of specific genes in addiction relevant behavioral and physiological traits (G. R. Uhl, Hall, & Sora, 2002; G. R. Uhl, et al., 2000). The first transgenic models, like the first candidate gene association studies, were based upon a priori assumptions about the importance of particular genes, including the main target molecules of morphine, amphetamine, and cocaine. This consequently emphasized the importance of monoamine transporters, opioid receptors, and monoamine receptors in addiction. In many cases these studies produced large effects on drug responses and behavior that might be considered to be relevant to addiction, but even these effects were complex and polygenic. As we shall see below, although the effects of opiates were, in many cases, eliminated in MOR KO mice, the case for psychostimulants was much more complex owing to an apparently more complex mechanism of action.
