Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys

beta-CIT (also designated RTI-55) is one of a series of 2 beta-carbomethoxy-3 beta-phenyltropane cocaine analogues that have recently been synthesized for characterizing the dopamine transporter and its function. The present study was designed to examine the behavioral effects of beta-CIT in rhesus monkeys. Two monkeys were allowed to self-administer cocaine (0.01 or 0.03 mg/kg/inj, IV, fixed-ratio 10, 1 h/day) in baseline sessions. When behavior was stable, beta-CIT (0.0007-0.003 mg/kg/inj, IV) was made available for self-administration for several consecutive sessions. beta-CIT maintained responding above saline levels in both monkeys. Two other monkeys were trained to discriminate cocaine (0.2 or 0.4 mg/kg, IM) from saline in a two-lever, food-reinforced drug discrimination paradigm. beta-CIT (0.012-0.025 mg/kg, IV) fully substituted for cocaine as a discriminative stimulus. In both preparations, beta-CIT was at least eightfold more potent than cocaine and had a longer duration of action. Thus, beta-CIT has cocaine-like behavioral effects indicative of a functional interaction with the dopamine transporter.