• transgenic;
  • knockout;
  • psychostimulant;
  • amphetamine;
  • cocaine

The first transgenic models used to study addiction were based upon a priori assumptions about the importance of particular genes in addiction, 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. Although the effects of opiates were largely eliminated by μ opioid receptor gene knockout, the case for psychostimulants was much more complex. Research using transgenic models supported the idea of a polygenic basis for psychostimulant effects and has associated particular genes with different behavioral consequences of psychostimulants. Phenotypic analysis of transgenic mice, especially gene knockout mice, has been instrumental in identifying the role of specific molecular targets of addictive drugs in their actions. In this article, we summarize studies that have provided insight into the polygenic determination of drug addiction phenotypes in ways that are not possible with other methods, emphasizing research into the effects of psychostimulant drugs in gene knockouts of the monoamine transporters and monoamine receptors.