Reinforcing and phencyclidine-like stimulus properties of enantiomers of metazocine.

The positive reinforcing properties of the racemate and stereoisomers of the benzomorphan, metazocine, were tested in three rhesus monkeys trained to self-administer IV injections of cocaine. The (-)-isomer maintained responding above saline levels at the highest dose tested (30 micrograms/kg/injection) in two of the three monkeys. Likewise, (+)-metazocine maintained self-administration responding in two monkeys at a dose of 100 micrograms/kg/injection. Responding for (+-)-metazocine was maintained in all three monkeys at doses of 10-100 micrograms/kg/injection. The discriminative stimulus properties of the three forms of metazocine were tested in rats trained to discriminate phencyclidine (PCP; 3.0 mg/kg) from saline on a two-lever food-reinforced operant task. When metazocine was tested in these animals, only the (+)-isomer produced dose-related increases in responding on the PCP-lever. Both (+-)- and (-)-metazocine resulted in only saline-appropriate responding. Thus, the results of these two experiments demonstrate that both enantiomers of metazocine function as positive reinforcers in monkeys and further, the reinforcing properties of (+)-metazocine may be due to the PCP/sigma properties of this isomer.