FURTHER EVALUATION OF THE REINFORCING EFFECTS OF THE NOVEL COCAINE ANALOG 2-BETA-PROPANOYL-3-BETA-(4-TOLYL)-TROPANE (PTT) IN RHESUS-MONKEYS

2 beta-Propanoyl-3 beta-(4-tolyl)-tropane (PTT) is a cocaine analog wh ich has been shown in rhesus monkeys to have cocaine-like discriminati ve stimulus effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys resp onding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the reinforcing effects o f PTT under a fixed-ratio (FR) schedule and to determine if decreasing the inter-injection interval would influence the reinforcing effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a mult iple FR 30 food-drug-food schedule. When responding was stable, cocain e (0.003-0.3 mg/kg per injection) or PTT (0.001-0.03 mg/kg per injecti on) was available during the drug component for at least five consecut ive sessions and until stable responding was observed. To investigate whether the inter-injection interval would influence PTT-maintained re sponse rates, the time-out (TO) following PTT injections was reduced f rom 180 or 300 s to 10 s for at least five consecutive sessions. Cocai ne-maintained response rates were characterized as an inverted-U shape d function of dose, with peak rates maintained by 0.03 mg/kg per injec tion cocaine. PTT (0.001-0.03 mg/kg per injection) maintained response rates significantly higher than rates maintained by the PTT vehicle, but significantly lower than cocaine-maintained response rates; PTT in take increased with dose. A reduction of the TO following PTT injectio ns to 10 s did not alter PTT-maintained response rates or total sessio n intake. Self-administered PTT was more potent than cocaine at decrea sing food-maintained responding. These results suggest that for long-a cting compounds like PTT, reinforcing effects are more likely to be ob served when the drug is available under a ratio-based schedule, compar ed to an interval-based schedule.