DCG-IV INHIBITS SYNAPTIC TRANSMISSION BY ACTIVATION OF NMDA RECEPTORSIN AREA CA1 OF RAT HIPPOCAMPUS

We investigated the synaptic depressant action of the metabotropic glu tamate receptor group II agonist, 'R,2'R,3'R)-2-(2',3'-dicarboxycyclop ropyl)-glycine (DCG-IV), in area CA1 of rat hippocampus. A brief bath application of DCG-IV (10 mu M) caused a rapidly reversible depression to 0.57 +/- 0.22 (i.e., 43%) of baseline excitatory postsynaptic pote ntial (epsp) slope. This depression could not be attenuated by the met abotropic glutamate receptor antagonists /(2S,3S,4S)-2-methyl-2-(carbo xycyclopropyl)glycine (MCCG), (RS)-alpha-methyl-4-tetrazolyphenylglyci ne (MTPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid alpha-methy l-AP4) (MAP4). However, the DCG-IV-induced depression could be reverse d by the NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic a cid (AP5; 50 mu M), and partially reversed by the adenosine A, recepto r antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 5 mu M) These results strongly suggest that DCG-IV is an agonist at NMDA receptors a nd provide further evidence against a role for metabotropic glutamate receptor group II in synaptic transmission in area CA1 of rat hippocam pus. (C) 1997 Elsevier Science B.V.