Differential effects of prototype opioid agonists on the acquisition of conditional discriminations in monkeys

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In each of two components of a multiple schedule, patas monkeys were required to respond on a right or left lever depending upon the stimulus combination (a color and a geometric form) presented. Reinforcement of a response in the presence of one stimulus (the form) was conditional upon the other stimulus (the color). The completion of a two-member chain of discriminations produced a food pellet. Errors produced a brief time-out. One component of the multiple schedule was a repeated-acquisition task where the discriminative stimuli for left- and right-lever responses changed each session (learning). In the other component, the discriminative stimuli were the same each session (performance). Morphine, ketocyclazocine and SKF 10,047 each produced dose-related decreases in overall rate of responding in both components of the multiple schedule. However, each drug affected the patterning of responding in a different manner. Across a range of doses which decreased response rate, neither morphine nor ketocyclazocine affected accuracy of the discriminations. In contrast, SKF 10,047 and its enantiomers produced a dose-dependent disruption of accuracy; errors were increased in the acquisition component at doses lower than those required to disrupt the discrimination in the performance component. The effects of the l-isomer of SKF 10,047 were generally comparable to those of the racemate. In comparison to the racemate, the d-isomer of SKF 10,047 was found to produce greater error-increasing effects in the acquisition component and smaller rate-decreasing effects in both components of the multiple schedule. In general, the effects of cyclazocine and pentazocine on both accuracy and rate of responding were comparable to those obtained with SKF 10,047. The results suggest that in patas monkeys, opioids with activity at the putative sigma receptor such as SKF 10,047, cyclazocine and pentazocine exert a dose-dependent disruptive effect on the accuracy of discriminations, an action not shared by prototypical mu and kappa opioid agonists, at doses which produce approximately equivalent rate-decreasing effects.

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Journal of Pharmacology and Experimental Therapeutics

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