Abstract
INHIBITION OF AMPA RECEPTORS AND ACTIVATION OF THE GLYCINE SITE OR POLYAMINE SITE OF NMDA RECEPTORS AT THE SUPRASPINAL LEVEL INDUCES ANTINOCICEPTION

Mitsumasa Matsuda, Masanobu Yoshikawa*, Takugi Kan, Xing Lu Jin, Shigeru Takahashi, Hiroyuki Kobayashi and Tomoki Nishiyama

ABSTRACT

At the supraspinal level, the role of AMPA receptors in the mechanism of pain remains to be fully clarified, even though they are found in large numbers throughout many brain regions. The results of this study revealed that intracerebroventricular administration of YM872, an AMPA receptor antagonist, exerted a dose-dependent antinociceptive effect on acute and tonic pain such as that induced by the tail flick or formalin tests without sedation or signs of abnormal behavior in rats. Moreover, the antinociceptive effect induced by intracerebroventricular administration of YM872 together with D-serine, an endogenous co-agonist for the glycine site of the NMDA receptor, or spermidine, an endogenous allosteric modulator for their polyamine site, was larger than that by application of YM872, D-serine, or spermidine alone in the formalin test. These results suggest that inhibition of AMPA receptors and/or activation of NR2B-containing NMDA receptors at the supraspinal level induces an antinociceptive effect on both acute and tonic pain.

Keywords: YM872, D-serine, spermidine, AMPA receptor, NMDA receptor.


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