DIFFERENTIAL MODULATION OF KAPPA-OPIOID AND MU-OPIOID ANTINOCICEPTION BY THE GLYCINE/NMDA RECEPTOR AGONIST D-SERINE

D-Serine, a selective agonist for the strychnine-insensitive glycine allosteric site associated with the NMDA receptor-ion channel complex, was found to modulate differentially the antinociception produced by Kappa and mu-opioid receptor agonists in the rat formalin test. D-Serine (100 mu g, i.c.v.) attenuated the antinociception produced by the selective Kappa-opioid agonist, enadoline (0.003-0.1 mg kg(-1), s.c.) against the tonic, but not acute, phase of the formalin response. Conversely, D-serine potentiated antinociception produced by morphine (0.3-10 mg kg(-1), s.c.) against both the acute and tonic phases. These results demonstrate an important interaction between the opioid and NMDA/glycine systems in the control of nociceptive information possibly at different levels of the neuraxis.