Abstract
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 δ- and μ-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 δ-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 μ-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 δ-opioid receptor agonists, whereas both reduced DAMGO-induced antinociception. These findings suggest that the supraspinal antinociceptive actions of μ- and δ-opioid receptor agonists appear to be modulated differently by NMDA and group I mGlu receptors in the mouse.
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