SELECTIVE DEPRESSION OF THE SPINAL POLYSYNAPTIC REFLEX BY THE NMDA RECEPTOR ANTAGONISTS IN AN ISOLATED SPINAL-CORD IN-VITRO

1. The effects of N-methyl-D-aspartate (NMDA) receptor glycine binding site antagonists 7-chlorokynurenate (7-Clkyn) and (+/-)-3-amino-1-hyd roxy-2-pyrrolidone (HA-966) on spinal reflexes in an isolated spinal c ord that was maintained in Mg2+-free medium in vitro were examined, Th e actions of 7-Clkyn and HA-966 were compared with those of the channe l site antagonist (i.e., dizocilpine) and NMDA-binding site antagonist s-that is, +/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) an d DL-2-amino-5-phosphonovalerate (APV). 2. 7-Clkyn and HA-966 produced a selective depression of the polysynaptic reflex (PSR) while negligi bly affecting the activity of the monosynaptic reflex (MSR). The PSR w as also differentially sup pressed by dizocilpine, CPP and APV. The PS R inhibitory activity of the NMDA antagonists was in the following ord er: dizocilpine>CPP>APV=7-Clkyn>HA-966. 3. The inhibitory effects of 7 -Clkyn on PSR were markedly antagonized by the simultaneous applicatio n of D-serine, an agonist for the NMDA receptor glycine-binding sites. However, PSR inhibition by dizocilpine and CPP was unaffected. 4. Inh ibition of the PSR by 7-Clkyn persisted in the presence of strychnine, which markedly increased the PSR activity by itself. 5. These finding s suggest that the NMDA receptor glycine-binding sites play a role in generating the NMDA receptor mediated PSR in the spinal cord in vitro. (C) 1997 Elsevier Science Inc.