Cocaine is a potent inhibitor of monoamine uptake in the central nervous system, thereby potentiating the neurochemical actions of dopamine, serotonin, and norepinephrine. Many proposed medications for cocaine abuse have focused on substitute therapies, but it is also important to understand the physiological changes that occur to the dopamine transporter during acquisition and repeated use of cocaine. It is possible that these changes may be involved in the maintenance of cocaine use and cocaine withdrawal after termination of its use. The purpose of this study is to examine changes in the dopamine transporter after repeated cocaine treatment and withdrawal in the rat using both biochemical and behavioral methods. In these studies, turnover of dopamine transporter binding and dopamine uptake in the rat will be measured after acute and repeated cocaine administration as well as after withdrawal. In order to characterize changes in dopamine transporter function in squirrel monkeys, we will use in vivo microdialysis to measure dopamine levels before, during acquisition and maintenance of cocaine self-administration, and during cocaine abstinence. Our hypothesis is that changes in dopamine transporters are correlated with acquisition and repeated use of cocaine and cocaine withdrawal. If changes in the dopamine transporter function are indeed involved in the acquisition of cocaine use and cocaine withdrawal, then development of medications that could offset or revert these changes would be useful in maintaining cocaine abstinence.
