Substitution and antagonism in rats trained to discriminate (+)-N- allylnormetazocine from saline

RL Balster

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.

(+)-N-Allylnormetazocine (NANM) binds to at least two sites in the mammalian central nervous system, a high-affinity, haloperidol- sensitive site and a lower-affinity site identified as the phencyclidine (PCP) receptor. The relevance of these sites to the discriminative stimulus properties of (+)-NANM was evaluated in rats trained to discriminate (+)-NANM from saline. Drugs with a high affinity for the haloperidol-sensitive site, including haloperidol, (+)- ketocyclazocine, 1,3-di-ortho-tolyl-guanidine and (-)-butaclamol failed to substitute for the (+)-NANM stimulus. In addition, when they were tested in combination with (+)-NANM, only haloperidol evidenced any antagonistic effects. The antagonistic effects of haloperidol were incomplete and only occurred at doses that substantially disrupted responding. Evidence obtained earlier that (+)-3-(3-hydroxyphenyl)-N-(1- propyl) piperidine could antagonize (+)-NANM was not replicated. On the other hand, PCP-like drugs from diverse chemical classes, including PCP, ketamine, MK-801, (-)-2-methyl-3,3-diphenyl-3-propanolamine, etoxadrol and dextrorphan, all substituted fully for the (+)-NANM stimulus with a potency predicted by their relative potency for PCP- like discriminative stimulus effects and relative affinity for the PCP receptor. Taken together, these results fail to provide evidence for an important role for the high-affinity haloperidol-sensitive binding site for (+)-NANM in its discriminative stimulus properties. Instead, activity at the PCP receptor is predictive of (+)-NANM-like effects.

Volume 249, Issue 3, pp. 749-756, 06/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				S. R. Engel, R. H. Purdy, and K. A. Grant Characterization of Discriminative Stimulus Effects of the Neuroactive Steroid Pregnanolone J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 489 - 495. [Abstract] [Full Text]

				S. A. Vanecek, W. D. Essman, D. P. Taylor, and J. H. Woods Discriminative Stimulus Characteristics of BMY 14802 in the Pigeon J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 1 - 9. [Abstract] [Full Text]