ABSTRACT Little et al., 1993 Little et al., , 1999 Staley et al., 1994) , accompanied by up-regulation of dopamine uptake Understanding the mechanisms involved in DAT binding site changes is important because 1) binding site alterations are the primary alterations documented in postmortem brain from cocaine users; 2) DAT inhibitors/ligands are being developed extensively as both therapeutic and imaging agents for both the DAT as well as dopamine neurons; and 3) DAT regulation may provide broader insights into the pharmacological effects of drugs on transporter binding sites. In addition to our need to uncover cocaine's neurochemical effects that provoke symptoms associated with its dependence, it is possible that new therapeutic or imaging agents (many of which are often DAT uptake inhibitors) might themselves induce adaptations in DAT function, as well as alter cocaine's effect on dopamine uptake. Also, potentially, DAT inhibitor binding sites could be altered through some mechanism that is independent of changes in DAT concentration or function
