Selective depression of the segmental polysynaptic reflex by phencyclidine and its analogs in the rat in vitro: interaction with N- methyl-D-aspartate receptors

Y Ohno and JE Warnick

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore.

The differential sensitivity of monosynaptic and polysynaptic reflexes to phencyclidine (PCP) and its analogs was examined in a Mg+(+)-free physiological solution using an in vitro spinal cord preparation of neonatal rats. Whereas the monosynaptic reflex was relatively resistant to N-methyl-D-aspartate antagonists [Mg++, 2-amino-5-phosphonovalerate (APV) and 2-amino-7-phosphonoheptanoate (AP7)], the polysynaptic reflex was markedly reduced in a concentration-dependent manner. The magnitude of the monosynaptic reflex only decreased 20 to 30% at concentrations of Mg++ (1.3 mM), APV (10 microM) and AP (10 microM), which completely depressed the polysynaptic reflex. PCP and its analogs also selectively depressed the polysynaptic reflex in a concentration-dependent manner and had relative potencies consistent with those for the PCP receptor [i.e., 1-(1-m-amino-phenylcyclohexyl)piperidine = MK-801 [(+)-5-methyl- 10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate] greater than 1-[1-(2-thienyl)cyclohexyl]piperidine greater than or equal to PCP much greater than (+)-N-allylnormetazocine much greater than 1-(1-m- nitrophenylcyclohexyl)piperidine. The latter compounds depressed the monosynaptic reflex to the same extent as Mg++, APV and AP7 at concentrations which completely depressed the polysynaptic reflex. Furthermore, the depression of the reflexes by PCP was unaffected by haloperidol and methiothepin precluding the involvement of sigma and serotonin receptors in PCP-induced depression of the polysynaptic reflex. Our results suggest that PCP and its analogs selectively depressed the polysynaptic reflex through PCP receptors associated with the N-methyl-D-aspartate receptor complex.

Volume 252, Issue 1, pp. 246-252, 01/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics