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.
Kest
B
B
Department of Psychology, University of California, Los Angeles 90024.
Marek
P
P
Liebeskind
J C
JC
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D011759:Pyrrolidines / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000700:Analgesics; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D016291:Dizocilpine Maleate; D009020:Morphine