COMPARISON OF A NOVEL TROPANE ANALOG OF COCAINE, 2-BETA-PROPANOYL-3-BETA-(4-TOLYL) TROPANE WITH COCAINE HCL IN RATS - NUCLEUS-ACCUMBENS EXTRACELLULAR DOPAMINE CONCENTRATION AND MOTOR-ACTIVITY

2 beta-propanoyl-3 beta-(4-tolyl) tropane (PTT) is a novel tropane tha t has been shown to be approximately 20 times more potent than cocaine in binding to the 3 beta-[4'-iodophenyl] tropane-2 beta-carboxylic ac id methyl ester (RTI-55) site on the dopamine transporter, an effect p artially attributable to the methyl constituent at the para position o n the phenyl ring. In addition, PTT lacks the eater linkage of cocaine , thus increasing its metabolic stability. This study was undertaken t o compare the quantitative and temporal effects of PTT and cocaine on in vivo neurochemical measures and motor behavior. The effects of PTT (0.3, 1.0 and 3.0 mg/kg; i.p.) and cocaine HCl (3.0, 10.0, and 30.0 mg /kg; i.p.) on nucleus accumbens extracellular dopamine concentrations [DA](e) were evaluated using in vivo microdialysis. Locomotor activity and stereotypic behaviors were also assessed. PTT and cocaine increas ed [DA](e) and total locomotor activity in a dose-dependent manner wit h PTT approximately 30 times more potent than cocaine. The relationshi p between [DA](e) and locomotor activity was linear over the test sess ion for cocaine, but not for PTT. In a subsequent experiment, pronounc ed stereotypic behaviors were evident in rats administered cocaine (10 .0 and 30.0 mg/kg) or PTT (3.0 mg/kg). The stereotypy elicited by PTT was longer in duration and greater in intensity than that elicited by the highest dose of cocaine. These results extend previously published data by demonstrating similar in vivo potencies for PTT on nucleus ac cumbens [DA](e) and locomotor activity. However, these data do not sup port the hypothesis that the time course of increased nucleus accumben s [DA](e) and stimulated locomotor activity are related.