A NOVEL METABOTROPIC GLUTAMATE-RECEPTOR AGONIST - MARKED DEPRESSION OF MONOSYNAPTIC EXCITATION IN THE NEWBORN RAT ISOLATED SPINAL-CORD

1 Neuropharmacological actions of a novel metabotropic glutamate receptor agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), were examined in the isolated spinal cord of the newborn rat, and compared with those of the established agonists of (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1) or (1S,3R)-l-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD). 2 At concentrations higher than 10 muM, DCG-IV caused a depolarization which was completely blocked by selective N-methyl-D-aspartate (NMDA) antagonists. The depolarization was pharmacologically quite different from that caused by L-CCG-1 and (IS,3R)-ACPD. 3 DCG-IV reduced the monosynaptic excitation of motoneurones rather than polysynaptic discharges in the nanomolar range without causing postsynaptic depolarization of motoneurones. DCG-IV was more effective than L-CCG-1, (IS,3R)-ACPD or L-2-amino-4-phosphonobutanoic acid (L-AP4) in reducing the monosynaptic excitation of motoneurones. 4 DCG-IV (30 nm-1 muM) did not depress the depolarization induced by known excitatory amino acids in the newborn rat motoneurones, but depressed the baseline fluctuation of the potential derived from ventral roots. Therefore, DCG-IV seems to reduce preferentially transmitter release from primary afferent nerve terminals. 5 Depression of monosynaptic excitation caused by DCG-IV was not affected by any known pharmacological agents, including 2-amino-3-phosphonopropanoic acid (AP3), diazepam, 2-hydroxysaclofen, picrotoxin and strychnine. 6 DCG-IV has the potential of providing further useful information on the physiological function of metabotropic glutamate receptors.