Activation of Supraspinal Nmda Receptors by Both D-serine Alone or in Combination with Morphine Leads to the Potentiation of Antinociception in Tail-flick Test of Rats.
From: Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan.
European journal of pharmacology
- Publish Date: Jun 2007
- ISSN: 0014-2999
- Volume: 565
- Issue: 1-3
- Pages: 89-97
- Medium: Print
- Language: English
- Citation (JAMA): Yoshikawa Masanobu, Ito Kenji, Maeda Miho, et al. Activation of Supraspinal Nmda Receptors by Both D-serine Alone or in Combination with Morphine Leads to the Potentiation of Antinociception in Tail-flick Test of Rats.. Eur. J. Pharmacol. Jun 2007;565:89-97
Abstract
Although there is a variety of information concerning the effects of the N-methyl-D-aspartate (NMDA) receptor on opioid-induced antinociception at the spinal level, little is known about the effects at the supraspinal level. To clarify the role of the NMDA receptor on the morphine-induced antinociception at the supraspinal level, we investigated the effects of the intracerebroventricular (i.c.v.) administration of D-serine, a selective agonist for the glycine site of the NMDA receptors, alone or in combination with morphine using the tail-flick test. The i.c.v. administration of D-serine, but not L-serine, alone produced a dose-dependent antinociception in the tail-flick response. D-Serine also dose-dependently potentiated the antinociceptive effect induced by the i.c.v. administration of morphine and the simultaneous administration produced an additive effect. The potentiation of the antinociception produced by both D-serine alone or in combination with morphine was dose-dependently attenuated by the i.c.v. administration of L-701,324, a selective antagonist for the glycine site of the NMDA receptors. In addition, the potentiation of the D-serine-induced antinociception was antagonized by the i.c.v. administration of naloxone, a nonselective opioid receptor antagonist. These observations, together with the fact that D-serine is an endogenous and selective co-agonist for the glycine site of the NMDA receptors, strongly suggested that the activation of the supraspinal NMDA receptors by D-serine leads to the potentiation of the antinociception in the tail-flick test and that endogenous D-serine could modulate the mu-opioid receptor mediated antinociception via the glycine site of the NMDA receptors at the supraspinal level.
Mesh Headings (Keywords): Analgesics, Animals, Drug Synergism, Male, Morphine, Naloxone, Pain Measurement, Quinolones, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate, Receptors, Opioid, mu, Serine, Spinal Cord, Stereoisomerism
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