THE NMDA ANTAGONIST 3-(2-CARBOXYPIPERAZIN-4-YL)PROPYL-1-PHOSPHONIC ACID (CPP) HAS ANTINOCICEPTIVE EFFECT AFTER INTRATHECAL INJECTION IN THERAT

This behavioral study was performed in order to delineate the antinoci ceptive effects of and the influence on motor function of a highly pot ent, competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)p ropyl-l-phosphonic acid (CPP). After intrathecal (i.t.) administration of CPP to chronically catheterized rats, antinociception was studied in 3 different nociceptive tests: the tail-flick test, the hot-plate t est, and the formalin test. The lowest dose producing visible motor dy sfunction was 1 nmol, with 2 of 8 animals showing slight ataxia. Dose- related motor dysfunction and apparent sedation was present after 5 an d 10 nmol. Dose-related antinociception was evident in the thermal tes ts following doses that produced little or no motor dysfunction. In th e tail-flick test, the antinociceptive effect was attenuated at higher doses, resulting in a bell-shaped dose-response relationship. Dose-re lated antinociception was found in both the first and second phase of the formalin test following doses from 0.25 up to 1 nmol. The present study shows that the competitive NMDA antagonist CPP has an antinocice ptive effect in doses that do not affect motor function. Furthermore, antinociception was evident in both phasic and tonic nociceptive tests . Finally, the dose-response relationship in the tail-flick test was b ell-shaped. As discussed this indicates that NMDA receptors may be inv olved in functionally divergent nociceptive systems.