Differential modulation of kappa 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 micrograms, 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 the 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.
Department of Biology, Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge.
J C
JC
Hunter
P
P
Atwal
G N
GN
Woodruff
L
L
Singh
D000698:Analgesia; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000502:physiology; D012694:Serine / Q000494:pharmacology*
D001572:Benzofurans; D011759:Pyrrolidines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012694:Serine; D009020:Morphine; C067110:enadoline