METABOTROPIC GLUTAMATE-RECEPTOR ANTAGONISTS, LIKE GABA(B) ANTAGONISTS, POTENTIATE DORSAL ROOT-EVOKED EXCITATORY SYNAPTIC TRANSMISSION AT NEONATAL RAT SPINAL MOTONEURONS IN-VITRO

Recordings of whole-cell synaptic current responses elicited by electr ical stimulation of dorsal roots were made from motoneurons, identifie d by antidromic invasion, in isolated spinal cord preparations from fi ve- to eight-day-old Wistar rats. Supramaximal electrical stimulation of the dorsal root evoked complex excitatory postsynaptic currents wit h mean latencies (+/- S.E.M.) of 6.1 +/- 0.26 ms, peak amplitude of - 650 +/- 47 pA and duration of 4.30 +/- 0.46 s (n=34). All phases of ex citatory postsynaptic currents were potentiated to approximately 20% a bove control levels in the presence of the metabotropic glutamate rece ptor antagonists S-2-amino-2-methyl-4-phosphonobutanoate (MAP4; 200 mu M; n=15) and 2S,1'S,2'S-2-methyl-2-(carboxycyclopropyl)glycine (MCCG; 200 mu M; n=9). A similar level of potentiation was produced by the G ABA(B) recept or antagonist thyl]amino-2-(S)-hydroxypropyl-P-benzyl-ph osphinic acid (CGP55845; 200 nM; n=5). MAP4 (200 mu M) produced a six- fold rightward shift in the concentration-effect plot for the depressa nt action of the metabotropic glutamate receptor agonist S-2-amino-4-p hosphonobutanoate (L-AP4), whereas CGP55845 produced no significant ch ange in the potency of L-AP4. MAP4 did not antagonize the depressant a ctions of baclofen (n=8), 1S,3S-1-aminocyclopentane-1,3-dicarboxylate (n=4) or 2-S,1'S,2'S-2-(carboxycyclopropyl)glycine (n=4). The metabotr opic glutamate receptor antagonists produced no change in the holding current of any of the neurons, indicating that they had no significant postsynaptic excitatory actions. These results are the first to indic ate a possible physiological role for metabotropic glutamate receptors in the spinal cord. Like GABA(B) receptors, they control glutamatergi c synaptic transmission in the segmental spinal pathway to motoneurons . This is likely to be a presynaptic control mechanism. (C) 1997 IBRO.