Non-NMDA receptor antagonist attenuates antinociception induced by morphine but not beta-endorphin, D-Pen2-D-Pen5-enkephalin, and U50, 488H administered intracerebroventricularly in mice.

The antinociception induced by morphine but not beta-endorphin, D-Pen2-D-Pen5-enkephalin (DPDPE), or U50, 488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide) administered intracerebroventricularly (i.c.v.) has been previously demonstrated to be mediated by the N-Methyl-D-Aspartic Acid (NMDA) receptor. The present study was designed to determine if non-NMDA receptors are involved in opioid-induced antinociception. Antinociception was assessed by the tail-flick test in male ICR mice. Various doses of CNQX (6-Cyano-7-nitroquinoxaline-2,3-dione), a competitive non-NMDA receptor antagonist, (0.001 to 0.5 microgram) injected intracerebroventricularly (i.c.v.) alone did not show any antinociceptive effect. CNQX (0.01 to 1 micrograms, i.c.v.) dose-dependently attenuated the inhibition of the tail-flick response induced by morphine (1 microgram). However, inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin (1 microgram), DPDPE (10 micrograms), or U50, 488H was not affected by i.c.v. administered CNQX. It is concluded that non-NMDA receptors are involved in i.c.v. morphine-induced antinociception. However, non-NMDA receptors are not involved in i.c.v. administered beta-endorphin-, DPDPE-, and U50, 488H-induced antinociception at the supraspinal level.