Dopamine Transporter--Structure/function Studies

National Institute On Drug Abuse

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Abstract

The dopamine transporter (DAT) has been a principal brain receptor site that has been correlated with the rewarding and euphoric properties of cocaine. MNB scientists cloned the DAT cDNA and gene, and found that deletion of both DAT and SERT are required to eliminate cocaine conditioned place preferences in mice. DAT is required for the actions of each of the current dopamine-selective toxins that produce the best models of Parkinson's disease. Analyses of DAT structure- function relationships, and their relationships with SERT, continued during this year with further characterization of promoter region haplotypes and their roles in level of expresion variaiton in vivo. Studies also characterized the effects of rare amino acid changes of interest in the dopamine transporter identified in human studies. Studies frefined the definition of 3' and 5'DAT haplotypes and have worked to correlate common 5' haplotype variants with levels of DAT expression in vivo in imaging and postmortem human tissue studies. These insights should continue to help in identification of structure-function relationships relevant to DAT regulation and human individual differences in DAT levels of expression and pharmacology.