Supraspinal NMDA and non-NMDA receptors are differentially involved in theproduction of antinociception by morphine and beta-endorphin administered intracerebroventricularly in the formalin pain model

Our previous studies have demonstrated that supraspinal glutamate receptors are differentially involved in the antinociception induced by morphine and beta -endorphin given intracerebroventricularly (i.c.v.) in the tail-flick and hotplate tests. The formalin pain test was used in the present study. Injection of mice with formalin solution (2%, 10 mul) into the hindpaw intr aplantarly produced the first (0-5 min) and second (20-40 min) phases of fo rmalin responses. The formalin responses in the both phases were attenuated dose-dependently by morphine (0.125-1 mug) or beta -endorphin (0.125-1 mug ) administered i.c.v. 5 min before. The antinociceptive effect of morphine was slightly more potent in the second phase whereas the effect of beta -en dorphin was more pronounced in the first phase. MK-801 (0.1-1 mug), a non-c ompetitive NMDA receptor antagonist, and CNQX (0.05-0.5 mug), a non-NMDA an tagonist, given i.c.v., produced antinociceptive effect in the both phases, but only in a partial manner. Both MK-801 (0.05 mug) and CNQX (0.01 mug), at the dose which had no intrinsic effect, reversed the antinociceptive eff ect of beta -endorphin (1 mug) observed during the second, but not the firs t, phase partially but significantly. However, the antinociceptive effect o f morphine (1 mug) was not affected by the same dose of MK-801 or CNQX give n i.c.v. Our results indicate that, at the supraspinal level, both NMDA and non-NMDA receptors are involved in the production of antinociception induc ed by supraspinally administered beta -endorphin, but not morphine, in the formalin pain model. (C) 2000 Harcourt Publishers Ltd.