THE REINFORCING AND DISCRIMINATIVE STIMULUS EFFECTS OF THE NOVEL COCAINE ANALOG 2-BETA-PROPANOYL-3-BETA-(4-TOLYL)-TROPANE IN RHESUS-MONKEYS

2 beta-propanoyl-3 beta-(4-tolyl)-tropane (PTT), is a cocaine analog t hat inhibits dopamine uptake, binding with high affinity and selectivi ty to the dopamine transporter. In the present study, the behavioral e ffects of PTT were evaluated in two models of cocaine abuse: drug self -administration and drug discrimination. In the first experiment, rhes us monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0 .1 mg/kg/injection, i.v.) under a fixed-interval 5-min schedule. Prese ssion administration of PTT (0.03-0.3 mg/kg, i.v.) or cocaine (0.3-3.0 mg/kg, i.v.) were evaluated. At both self-administered doses of cocai ne, PTT decreased response rates and total session intakes and was app roximately 0.5 to 1.0 log units more potent than cocaine. In experimen t 2, the reinforcing effects of PTT (0.003-0.1 mg/kg/injection) were e valuated in a separate group of monkeys (n = 4) responding under a fix ed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentat ion. When substituted for cocaine, PTT maintained response rates simil ar to saline-maintained rates and significantly lower than rates maint ained by cocaine (0.003-0.3 mg/kg/injection). Total session PTT intake was significantly lower than cocaine intake. In experiment 3, the dis criminative stimulus effects of PTT (0.003-0.1 mg/kg, i.m.) were evalu ated in monkeys (n = 3) trained to discriminate cocaine (0.2 mg/kg, i. m.) from saline (0.5 ml). PTT substituted for cocaine in a dose-depend ent manner and was 0.5 to 1.0 log units more potent than cocaine. At t he highest PTT dose, cocaine-appropriate responding was observed 8 to 24 hr after the injection. These results demonstrated that the long-ac ting indirect dopamine agonist PTT was effective in decreasing cocaine self-administration and in abuse liability testing showed a unique be havioral profile, not functioning as a reinforcer when substituted for cocaine and producing discriminative stimulus effects similar to coca ine.