DCG-IV inhibits synaptic transmission by activation of NMDA receptors in area CA1 of rat hippocampus

We investigated the synaptic depressant action of the metabotropic glutamate receptor group II agonist, (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-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 potential (epsp) slope. This depression could not be attenuated by the metabotropic glutamate receptor antagonists alpha-methyl-L-CCGI/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG), (RS)-alpha-methyl-4-tetrazolyphenylglycine (MTPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid alpha-methyl-AP4) (MAP4). However, the DCG-IV-induced depression could be reversed by the NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 mu M), and partially reversed by the adenosine A, receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 5 mu M) These results strongly suggest that DCG-IV is an agonist at NMDA receptors and provide further evidence against a role for metabotropic glutamate receptor group II in synaptic transmission in area CA1 of rat hippocampus. (C) 1997 Elsevier Science B.V.