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

Abstract

We investigated the synaptic depressant action of the metabotropic glutamate receptor group II agonist, (2 S,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 μM) 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 α-methyl- l-CCGI/(2 S,3 S,4 S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG), ( R S)-α-methyl-4-tetrazolyphenylglycine (MTPG) or ( S)-2-amino-2-methyl-4-phosphonobutanoic acid α-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 μM), and partially reversed by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 5 μM). 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. © 1997 Elsevier Science B.V. All rights reserved.