Self-administration of two long-acting monoamine transport blockers in rhesus monkeys

Rationale: 2 beta -propanoyl-3 beta-(4-tolyl)-tropane (PTT) is a cocaine an alog with high affinity at and selectivity for the dopamine transporter (DA T). 2 beta -propanoyl-3 beta-(2-naphthyl)-tropane (HD-23), like cocaine, bi nds with approximately equal affinity to the DAT, the serotonin transporter , and the norepinephrine transporter but has over a 100-fold higher affinit y for these monoamine transporters than cocaine. The reinforcing effects of these drugs have not been evaluated in cocaine-na nonhuman primates. Objec tive: The primary goal of the present study was to examine the reinforcing effects of PTT and HD-23 in rhesus monkeys before and after a history of in travenous cocaine self-administration. Methods: Monkeys (n=4) were initiall y trained to respond under a fixed-ratio 30 schedule of food presentation. When responding was stable, saline, PTT (0.001-0.03 mg/kg per injection), a nd HD-23 (0.0003-0.0056 mg/kg per injection) were made available fur self-a dministration fur least five sessions per dose. Next, a cocaine dose-effect function (0.0003-0.3 mg/kg per injection) was determined and then PTT and HD-23 dose-effect curves were redetermined. Results: When substituted for f ood, neither drug maintained responding significantly higher than saline du ring 3-h (PTT and HD-23) or 22-h (PTT) sessions. After determining the coca ine dose-effect function, PTT and HD-23 functioned as reinforcers in one of four monkeys, when substituted for food during daily 3-h sessions. However , when PTT was made available during 22-h sessions, it had reinforcing effe cts in three of the four monkeys tested. Conclusions: These results indicat e that the reinforcing effects: of PTT were slightly modified by a brief hi story of cocaine reinforcement, and that the weak reinforcing effects were most apparent when the drug was available under unlimited-access conditions .