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

Abstract.

Rationale: 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) is a cocaine analog with high affinity at and selectivity for the dopamine transporter (DAT). 2β-propanoyl-3β-(2-naphthyl)-tropane (HD-23), like cocaine, binds with approximately equal affinity to the DAT, the serotonin transporter, and the norepinephrine transporter but has over a 100-fold higher affinity for these monoamine transporters than cocaine. The reinforcing effects of these drugs have not been evaluated in cocaine-naïve non-human primates. Objective: 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 intravenous cocaine self-administration. Methods: Monkeys (n=4) were initially 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), and HD-23 (0.0003–0.0056 mg/kg per injection) were made available for self-administration for 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 food, neither drug maintained responding significantly higher than saline during 3-h (PTT and HD-23) or 22-h (PTT) sessions. After determining the cocaine 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 effects in three of the four monkeys tested. Conclusions: These results indicate that the reinforcing effects of PTT were slightly modified by a brief history of cocaine reinforcement, and that the weak reinforcing effects were most apparent when the drug was available under unlimited-access conditions.