Phenotypic analysis of transgenic mice, in particular those utilizing KO mice, have greatly contributed to our understanding of the molecular mechanisms of drugs of abuse. As initial candidate gene studies began to find evidence supporting the roles of a number of monoaminergic genes, in particular, in the genetic component of addiction liability, KO studies were conducted, in part, to confirm the importance of these genes in the effects of drugs of abuse, and by implication, addiction. Thus, early efforts to examine the roles of genes in addiction using transgenic techniques targeted what were thought to be the main targets of opiates (MOR), cocaine (DAT) and amphetamine (the vesicular monoamine transporter; VMAT2).