Discriminative stimulus properties of (+)- and (-)-n allylnormetazocine: the role of training dose in the stimulus substitution patterns produced by PCP/sigma and mixed action opioid compounds.

The discriminative stimulus effects of the stereoisomers of N-allylnormetazocine (NANM) were evaluated in separate groups of pigeons trained to discriminate 3.0 (low) then 7.5 (high) mg/kg (-)-NANM from saline or 3.0 (high) then 1.0 (low) mg/kg (+)-NANM from saline. The stimulus effects of the high and low training dose of (-)-NANM were shared by the PCP/sigma compounds (+)-NANM, phencyclidine, dextrorphan, (+)-cyclazocine and (+)-metazocine but not the putative sigma ligand (+)-pentazocine. Doses of naloxone 3-10 times larger than those which antagonize the effects of mu and kappa opioids failed to alter these substitution patterns. In contrast to the lack of substitution obtained with the mu opioid morphine, kappa opioid bremazocine and opioid antagonist naloxone, the mixed action opioids (-)-pentazocine, butorphanol, nalbuphine and nalorphine substituted completely for the low training dose and partially for the high training dose of (-)-NANM. At the low training dose, the substitution patterns produced by these mixed action opioids were naloxone-reversible. Complete substitution for both training doses of (-)-NANM was also obtained with the mixed action opioids levallorphan and (-)-cyclazocine, although these effects were not naloxone-reversible. In pigeons trained to discriminate the high and low training dose of (+)-NANM from saline, (-)-NANM and the PCP/sigma compounds substituted completely and in a non-naloxone reversible manner. The relative potencies of these PCP/sigma compounds in producing (+)-NANM-like stimulus effects were highly correlated with their relative affinity for the sites labeled by PCP but not (+)-NANM. In these pigeons, naloxone revealed the (+)-NANM-like stimulus effects produced by (-)-pentazocine and (-)-cyclazocine, thus suggesting that these mixed action opioids have a prominent PCP/sigma-like component. When administered alone or in combination with naloxone, the other mixed action opioids evaluated failed to substitute for either the high or low training dose of (+)-NANM. The present results indicate that the stimulus effects of both training doses of (+)-NANM and the high training dose of (-)-NANM are comprised of a PCP/sigma component, whereas that of the low training dose of (-)-NANM has both a PCP/sigma and a naloxone-reversible, opioid component.