Midbrain dopamine (DA) systems are involved in various motor and mental func-tions. Parkinson's disease results from the loss of nigrostriatal DA neurons, whereas over activity of the mesolimbic DA system is implicated in the development of psychiatric conditions such as schizophrenia. DA systems play a major role in mediating psychostimulant-induced behavioral changes, as well as mediating their rewarding properties. Methamphetamine (METH), an increasingly popular illicit amphetamine analog, can induce short- and long-lasting changes in DA and 5-hydroxytryptamine (5-HT) systems. Elevated concentrations of extracellular DA, caused by METH treatment, are thought to contribute to these monoaminergic changes due to the oxidative capacity of this catecholamine. This laboratory reported recently that METH administration induces a rapid and reversible diminution in dopamine transporter (DAT) function. Because DA can cause the formation of reactive oxygen species (ROS), and since it has been demonstrated that the DAT is altered by ROS, this METH-induced effect on DAT may be an oxidative consequence. Thus, the objective of this proposal is to test the hypothesis that DA-related ROS mediate the rapid and reversible change in striatal DAT function induced.
