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

The modulatory effects of mGlu receptors on NMDA‐induced potential changes in spinal motoneurones were studied in vitro . Selective activation of mGlu5 receptors by 10 μ M (RS)‐2‐Chloro‐5‐hydroxyphenylglycine (CHPG; EC 50 =280±24 μ M ) 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. The attenuating effect of CHPG on the NMDA‐induced VRD was inhibited by the mGluR5 receptor antagonist, 2‐methyl‐6‐phenyl‐ethynylpyridine (MPEP). 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. (2R,4R)‐4‐aminopyrrolidine‐2,4‐dicarboxylate ((2R,4R)‐APDC), a group II mGlu receptor agonist did not attenuate the NMDA‐induced response. 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.British Journal of Pharmacology (2002) 136 , 248–254; doi: 10.1038/sj.bjp.0704698