Stimulus properties of the narcotic antagonist pentazocine: similarity to morphine and antagonism by naloxone

Abstract

Pentazocine (10 mg/kg) and saline were used as discriminative stimuli in rats. After pentazocine administration, reinforcement could be obtained contingent on pressing one particular lever (left or right) in a two-lever operant chamber. Responding on the opposite lever was reinforced only after saline injections; a drug-lever combination was always held constant for each animal. Discriminated choice responding between pentazocine and saline was learned to an 80% correct criterion. Test injections of morphine produced dose-related responding on the pentazocine lever. Choice responding after 7.5 mg/kg of morphine was not significantly different from choice responding after 10 mg/kg of pentazocine. The discriminable ED50 values for both pentazocine and morphine were estimated from dose-response curves and when given in combination (pentazocine ED50 + morphine ED50), more drug-related responding occurred than occurred after either drug (ED50) alone. Naloxone produced saline-like responding but antagonized the stimulus properties of both pentazocine and morphine. However, the antagonism of the morphine cue by naloxone was significantly greater than the antagonism of the pentazocine cue. The results indicate that pentazocine and morphine are similar in at least one important respect suggesting that these drugs may share a common site of action.