SELF-ADMINISTRATION OF THE DOPAMINE D-3 AGONIST 7-OH-DPAT IN RHESUS-MONKEYS IS MODIFIED BY PRIOR COCAINE EXPOSURE

Cocaine self-administration was compared with responding maintained by the dopamine D-3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7 -OH-DPAT) in rhesus monkeys. In the first experiment, monkeys (n=3) wi th an extensive cocaine history responded under a fixed-interval (FI) 5-min schedule of IV cocaine (0.03 mg/kg per injection) presentation, during daily 4-h sessions. When responding was stable, dose-response c urves were determined for cocaine (0.01-0.3 mg/kg per injection) and 7 -OH-DPAT (0.001-0.1 mg/kg per injection); each dose was available for at least five consecutive sessions. When substituted for the baseline dose of cocaine, other doses of cocaine and 7-OH-DPAT maintained rates higher than responding maintained by saline injections, in all monkey s. 7-OH-DPAT maintained response rates equal to or higher than rates o f cocaine-maintained responding in all monkeys. In a second experiment , acquisition of 7-OH-DPAT self-administration was evaluated in a grou p of cocaine-naive monkeys (n=3). Various doses of 7-OH-DPAT (0.003-0. 03 mg/kg per injection) were available under an FI 15-s schedule durin g daily 4-h sessions. After 10-13 sessions, 7-OH-DPAT self-administrat ion could not be trained in any cocaine-naive monkey. When cocaine was made available to these monkeys, responding was reliably maintained w ithin one to four sessions and the schedule was gradually increased to FI 5-min. After stable responding under an FI 5-min schedule of 0.03 mg/kg per injection cocaine presentation, 7-OH-DPAT (0.01 mg/kg per in jection) was again made available to two of the monkeys, and maintaine d responding at rates higher than saline. To determine better whether a history of responding maintained by another reinforcer would result in high rates of 7-OH-DPAT self-administration, two cocaine-naive monk eys were trained to respond under an FI 5-min schedule of food present ation. Substituting 7-OH-DPAT (0.003-0.03 mg/kg per injection) for foo d resulted in very low rates of responding. Taken together, these resu lts suggest that despite comparable reinforcing effects in cocaine-sub stitution studies, 7-OH-DPAT and cocaine differ in their rate of acqui sition, perhaps indicating a lower abuse liability for 7-OH-DPAT.