Further characterization of the three-choice morphine, cyclazocine and saline discrimination paradigm: opioids with agonist and antagonist properties.
Rats were trained in a three-choice morphine (3.0 mg/kg), cyclazocine (0.3 mg/kg) and saline discrimination using a discrete-trials avoidance procedure. Behavior was considered to be under stimulus control when an animal reliably completed at least 18 trials of a 20-trial session on the correct lever after s.c. administration of either morphine, cyclazocine or saline. In tests of stimulus generalization, levorphanol produced a dose-related increase in trials completed on the morphine choice lever, whereas its optical enantiomer, dextrorphan, produced predominantly cyclazocine-appropriate responding, indicating that stimulus control of behavior was stereoselective. Ethylketocyclazocine, ketocyclazocine, levallorphan and SKF 10,047 engendered stimulus control of behavior that was unambiguously cyclazocine-like. In contrast, three other opioids with mixed agonist and antagonist properties occasioned responding on both the morphine- and cyclazocine-appropriate choice levers consistent with the mixture of morphine- and cyclazocine-like activity exhibited by these drugs in other procedures in animals and man. The stimulus effects of phencyclidine, a nonopioid compound, were not clearly interpretable within the present experimental context. This three-choice discrimination paradigm provides an approach for studying concurrently the morphine- and cyclazocine-like discriminative stimulus effects of opioids with multiple components of action and may lead to a more precise characterization of the stimulus properties of mixed-acting opioids than has been possible with conventional two-choice discrimination paradigms alone.
D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004193:Discrimination Learning; D004192:Discrimination, Psychological / Q000187:drug effects*; D016314:Ethylketocyclazocine / Q000031:analogs & derivatives; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D013237:Stereoisomerism
D009292:Narcotic Antagonists; D009294:Narcotics; D012965:Sodium Chloride; D016314:Ethylketocyclazocine; C012395:ketazocine; C012134:SK&F 10047; D009020:Morphine; D010620:Phenazocine; D010622:Phencyclidine; D003496:Cyclazocine