Discriminative stimulus properties of (+)-N-allylnormetazocine in the rat: correlations with (+)-N-allylnormetazocine and phencyclidine receptor binding.
Recent studies have identified a stereospecific (+)-NANM binding site that binds psychotomimetic opioids and phencyclidine (PCP) but has a distribution in brain different from the PCP binding site. Since (+)-NANM has no opioid activity and (-)-NANM has opioid activity, rats were trained to discriminate (+)-NANM from saline in order to develop an ability to distinguish the (+)-NANM cues from other opioid agonist and antagonist activities. Cyclazocine, PCP, and ketamine all produced (+)-NANM-like stimuli in a dose-dependent manner. Behaviorally, cyclazocine and PCP are equipotent to (+)-NANM whereas ketamine is 6.7 times less potent than (+)-NANM. Pentazocine had the highest affinity for the (+)-[3H]NANM binding site, yet did not produce (+)-NANM-like discriminative stimuli. By contrast, ketamine had the lowest binding affinity for the (+)-[3H]NANM binding site and did produce (+)-NANM-like discriminative stimuli. Drug discrimination potencies relative to (+)-NANM were not predictive of relative binding affinities at (+)-NANM or PCP binding sites, although there was a trend toward a stronger correlation with the PCP binding site. Therefore, the discriminative stimulus properties of (+)-NANM cannot be explained by pharmacologic actions at either (+)-NANM or PCP binding sites alone, and may involve concurrent actions at both sites.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003496:Cyclazocine / Q000494:pharmacology; D004193:Discrimination Learning; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010622:Phencyclidine / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013237:Stereoisomerism
D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D007649:Ketamine; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; D003496:Cyclazocine; D010423:Pentazocine