PT - JOURNAL ARTICLE AU - Joshua A. Lile AU - Drake Morgan AU - Anne M. Birmingham AU - Zhixia Wang AU - William L. Woolverton AU - Huw M. L. Davies AU - Michael A. Nader TI - The Reinforcing Efficacy of the Dopamine Reuptake Inhibitor 2β-Propanoyl-3β-(4-tolyl)-tropane (PTT) as Measured by a Progressive-Ratio Schedule and a Choice Procedure in Rhesus Monkeys AID - 10.1124/jpet.102.039180 DP - 2002 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 640--648 VI - 303 IP - 2 4099 - http://jpet.aspetjournals.org/content/303/2/640.short 4100 - http://jpet.aspetjournals.org/content/303/2/640.full SO - J Pharmacol Exp Ther2002 Nov 01; 303 AB - The present series of experiments was undertaken to investigate the variables that influence the reinforcing efficacy of psychostimulants. The time of onset for dopamine transporter (DAT) occupancy of the long-acting, high-affinity DAT blocker 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) was measured using an ex vivo binding assay in rodents and was determined to be significantly longer than for cocaine (30 min versus 2 min). To assess the reinforcing efficacy of PTT relative to cocaine, a discrete-trials drug-drug choice procedure (n = 3) and a progressive-ratio (PR) schedule (n = 4) were used in rhesus monkeys. Cocaine (0.003–0.56 mg/kg/injection) and PTT (0.003–0.03 mg/kg/injection) maintained responding greater than saline under the PR schedule. Maximal breaking points were significantly higher for cocaine compared with PTT. A separate group of monkeys prepared with double-lumen catheters was allowed to choose between cocaine (saline and 0.03–0.3 mg/kg/injection) and PTT (saline, and 0.01 and 0.03 mg/kg/injection). Under these conditions, PTT was not preferred over saline. When saline or 0.01 mg/kg/injection PTT was available as alternatives to cocaine, the highest dose of cocaine maintained greater than 80% choice. When 0.03 mg/kg/injection PTT was the alternative to cocaine, cocaine choice declined to approximately 50%, and total cocaine intake was decreased by ∼70% at the highest cocaine dose. These results suggest that the reinforcing efficacy of PTT is less than cocaine in nonhuman primates. Data from studies with PTT indicate that slow-onset, long-acting DAT inhibitors can decrease cocaine self-administration while not functioning robustly as reinforcers, and support the further investigation of these drugs as treatment for cocaine addiction. The American Society for Pharmacology and Experimental Therapeutics