An investigation of the negative-reinforcing properties of naloxone and cyclazocine in squirrel monkeys.

Monkeys were trained to emit 10 responses to terminate a schedule complex consisting of a light and masking noise in the presence of which brief, intravenous injections of naloxone (0.01 mg/kg per injection), dl-cyclazocine (0.003, 0.01 mg/kg per injection), or saline were scheduled to occur over blocks of consecutive daily sessions. Completion of the fixed ratio (FR 10) response requirement terminated the schedule complex, producing a time-out of 60 s in which responses were without consequence and injections did not occur. Sessions lasted for 100 min or ended after 100 injections, whichever came first. When monkeys received an intramuscular injection of morphine (10 mg/kg) 60 min preceding each session, responding to avoid injections of naloxone or cyclazocine was well maintained, though morphine-dependent monkeys tolerated injections of saline or the vehicle in which cyclazocine was dissolved. When the morphine pretreatment regimen was discontinued, monkeys tolerated injections of naloxone and cyclazocine though, at the larger cyclazocine dose (0.01 mg/kg per injection), responding was maintained for at least 30 consecutive sessions in two postdependent animals, but not in two other monkeys treated identically. The capacity of these morphine-antagonist drugs to support responding that avoids their injection depends evidently upon whether monkeys are rendered morphine dependent or not; in the case of cyclazocine, however, an increased sensitivity to the negative-reinforcing effects of the drug appears to persist in some "postdependent" monkeys.