Interaction of group I mGlu and NMDA receptor agonists within the dorsal horn of the spinal cord of the juvenile rat

Br J Pharmacol. 2002 May;136(2):248-54. doi: 10.1038/sj.bjp.0704698.


1. The modulatory effects of mGlu receptors on NMDA-induced potential changes in spinal motoneurones were studied in vitro. 2. Selective activation of mGlu5 receptors by 10 microM (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG; EC(50)=280 +/- 24 microM) did not produce any change in the ventral root potential. However, the same concentration of CHPG (10 min perfusion) significantly attenuated the NMDA-induced ventral root depolarization (VRD). The effect persisted for 10 min after washout. NMDA-induced responses returned to control in 30 min. Brief co-application of CHPG and NMDA did not alter the NMDA-induced response indicating lack of direct receptor interaction. 3. The attenuating effect of CHPG on the NMDA-induced VRD was inhibited by the mGluR5 receptor antagonist, 2-methyl-6-phenyl-ethynylpyridine (MPEP). 4. In the presence of CGP56433A, a GABA(B) receptor antagonist, the NMDA-induced VRD was unchanged. However, NMDA-induced responses were potentiated after 10 min co-application of CHPG and CGP56433A. 5. (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group II mGlu receptor agonist did not attenuate the NMDA-induced response. 6. Under normal physiological conditions group I mGlu receptor agonists activate at least two populations of neurones: (1) GABA-ergic cells, which could release GABA and inhibit dorsal horn neurones, and (2) deep dorsal horn neurones/motoneurones which express NMDA receptors. Therefore, activation of mGlu5 receptors located on GABA-ergic interneurones could influence any direct potentiating interaction between mGlu5 and NMDA receptors in spinal cord and result in depression of the VRD. In the presence of a GABA(B) receptor antagonist, the direct synergistic interaction is unmasked. These data suggest that group I mGlu receptors provide a complex modulation of spinal synaptic processes.

MeSH terms

  • Animals
  • Excitatory Amino Acid Agonists / pharmacology*
  • GABA-B Receptor Antagonists
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • In Vitro Techniques
  • Phenylacetates / pharmacology
  • Posterior Horn Cells / drug effects*
  • Posterior Horn Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / physiology
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / physiology
  • Receptors, N-Methyl-D-Aspartate / agonists*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • 2-chloro-5-hydroxyphenylglycine
  • Excitatory Amino Acid Agonists
  • GABA-B Receptor Antagonists
  • Phenylacetates
  • Receptors, GABA-B
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • metabotropic glutamate receptor type 1
  • Glycine