The overall objective of the proposed research is to characterize, on complex behavioral processes, the effects of different opioids which are either being tested or used therapeutically and are subject to abuse. Complex operant tasks involving learning and memory in nonhuman primates will be the major focus of investigation. A multiple schedule will be used in order to make a direct comparison of drug effects on the repeated acquistion and performance of conditional discriminations. A delayed conditional discrimination procedure will be used to evaluate drug effects on short-term memory. Finally, a fixed-ratio discrimation procedure will be used to test the effects of these drugs, in both primates and rats, in a situation where the discriminative stimulus is an aspect of the subject's own behavior. In the first series of experiments we will continue our studies of the acute effects of various opioids (e.g., buprenorphine, butorphanol, nalbuphine) and determine the extent to which the disruptive effects of other opioids (e.g., cyclazocine, methadone), on either rate or accuracy of responding, are stereo-specific. In a second series of experiments, acute doses of those opioids which disrupt accuracy (e.g., cyclazocine, meperidine, pentazocine) will be tested in combination with various doses of pharmacologiclly distinct antagonists (e.g., haloperidol, physostigmine) in order to determine whether the disruptive effects of these drugs may be mediated by a nonopioid mechanism(s) of action. In the third series of experiments different opioids, which do (e.g., cyclazocine, pentazocine) and do not (e.g., heroin, methadone) exert a disruptive effect on accuracy when administered alone, will be tested in combination with other prototypical drugs of abuse (d-amphetamine, lorazepam, pentobarbital). The purpose of these experiments will be to determine how the opioids, in combination with other drugs of abuse, affect learning and memory in nonhuman primates.
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