The dopamine transporter/cocaine receptor (DAT) is the site at which cocaine exerts rewarding/reinforcing effects. Recent cloning of the DAT cDNAs provided an opportunity to study the expression and regulation by psychostimulants of DAT mRNA in cells of rat and human brains, especially in cells implicated in central pathways of behavioral reward and reinforcement. In situ hybridization revealed that rat and human DAT mRNAs are expressed abundantly in neurons of the ventral tegmental area, the systems most implicated in studies of psychostimulant reward and reinforcement. Interestingly, expression levels are even higher in neurons of the substantia nigra, pars compacta, and lower in neurons of the arcuate nucleus. Northern analysis confirmed that a single DAT mRNA was distributed in this pattern. Rats treated acutely or chronically with the psychostimulant amphetamine displayed no significant alteration in levels of DAT mRNA in Northern analyses, despite significant alterations in other mRNAs in the same experiments. Preliminary in situ hybridization studies indicate possible small regional alterations in DAT mRNA following cocaine administration. These results demonstrate that the dopamine transporter cDNA cloned in the previous FY is expressed in rat and human neurons well-positioned to mediate cocaine and amphetamine psycho- and motor- stimulant effects. These data also suggest caution in using studies of arcuate hypothalamic dopamine systems that regulate prolactin as an accurate reflection of cocaine actions on ventral midbrain systems likely to be more directly implicated in psychomotor stimulation.
