The dopamine transporter (DAT) has been identified as a principal brain receptor site previously correlated with the rewarding and euphoric properties of cocaine. Euphoric responses to rapid administration of cocaine can be much more prominent than those that follow slower rates of administration. In previous years, investigators in this Branch have found that activators of protein kinase C (PKC) modulate dopamine transport in transiently-expressing COS cells. In the current year, we have followed previous observations that identified DAT as a phosphoprotein to identify efects on MAP kinase agents on dopamine upatke rates. Studies of site directed mutants in ppotential phosphoacceptor sites identify N-terminal mutants as important for MAP kinase, and for PKC regulation. These data increase evidence that PKC and MAP kinase regulation of DAT occurs through multiple direct- and indirect mechanisms.
