Cocaine, a psychomotor stimulant and local anesthetic, is a significant drug of abuse. Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. Specifically, cocaine binds to the dopamine transporter (DAT) and blocks the uptake of dopamine (DA). Additionally, the level binds to the dopamine transporter of DAT occupancy may be important in the reinforcing effects of cocaine and other DAT ligands. The purpose of this research in this proposal is to relate the reinforcing effects of cocaine and other DAT ligands. The purpose of the research in this proposal is to relate the reinforcing effects of cocaine. RTI 177, RTI 113 (phenyltropane analogs of cocaine) and procaine (a local anesthetic) to DAT occupancy in the striatum and increases in extracellular DA in the caudate nucleus and nucleus accumbens. The reinforcing potency and effectiveness (maximum reinforcing effect) of cocaine, RTI 177, RTI 113 and procaine will be studied using a second-order schedule of reinforcement in rhesus monkeys. DAT occupancy at maximum and equieffective doses for reinforcing effects will be determined during neuroimaging using positron emission tomography in rhesus monkeys. Additionally, the percent increase in extracellular DA will be determined at reinforcing doses of the drugs using in vivo microdialysis in rhesus monkeys. Finally, percent DAT occupancy will be related to percent increase in extracellular DA.
