Different effects of NMDA/group I metabotropic glutamate receptor agents in delta- and mu-opioid receptor agonist-induced supraspinal antinociception.
The N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mGlu) receptors are involved in nociceptive transmission in the central nervous system. The present study was designed to study the effects of NMDA and group I mGlu receptor agents on delta- and mu-opioid receptor agonist-induced antinociception in the mouse brain. Intracerebroventricular (i.c.v.) treatment with the non-competitive NMDA receptor antagonist dizocilpine and the group I mGlu receptor antagonist (S)-4-carboxyphenylglycine ((S)-4CPG) significantly attenuated the antinociception induced by the delta-opioid receptor agonists [D-Pen(2), Pen(5)]enkephalin (DPDPE), (-)-TAN 67 and [D-Ala(2)]deltorphin II. On the contrary, i.c.v. administration of dizocilpine and (S)-4CPG slightly but significantly enhanced the antinociception induced by the mu-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO). Under these conditions, i.c.v. administration of NMDA and the group I mGlu receptor agonist 3,5-dihydrophenylglycine (DHPG) significantly enhanced the antinociception induced by delta-opioid receptor agonists, whereas both reduced DAMGO-induced antinociception. These findings suggest that the supraspinal antinociceptive actions of mu- and delta-opioid receptor agonists appear to be modulated differently by NMDA and group I mGlu receptors in the mouse.
Suzuki
T
T
Department of Toxicology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan. suzuki@hoshi.ac.jp
Aoki
T
T
Ohnishi
O
O
Nagase
H
H
Narita
M
M
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*
D000700:Analgesics; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D009842:Oligopeptides; D011804:Quinolines; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C094142:TAN 67; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; C079693:4-carboxyphenylglycine; D020881:Enkephalin, D-Penicillamine (2,5)-; D005998:Glycine