The specific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocks U-50,488, but not morphine antinociception.

The effect of the specific NMDA receptor antagonist MK-801 on antinociception produced by the kappa opiate receptor agonist U-50,488 and the mu receptor agonist morphine was assessed using the tail-flick test in rats. MK-801 (0.05 and 0.1 mg/kg) antagonized antinociception induced by all three doses of U-50,488 (7.5, 15 and 30 mg/kg), and potentiated antinociception induced by the lower (1 mg/kg) but not higher (5 mg/kg) dose of morphine. Naloxone at a dose of 1.0 but not 0.1 mg/kg blocked U-50,488 antinociception, indicating that MK-801 affects opiate antinociception. The present results are the first to suggest a critical role for the NMDA receptor in opiate antinociception involving the kappa receptor.