(+)-MCPG Blocks Induction of LTP in CA1 of Rat Hippocampus via Agonist Action at an mGluR Group II Receptor

Abstract

Breakwell, N. A., M. J. Rowan, and R. Anwyl. (+)-MCPG blocks induction of LTP in CA1 of rat hippocampus via agonist action at an mGluR group II receptor. J. Neurophysiol. 79: 1270–1276, 1998. We investigated the effect of metabotropic glutamate receptor (mGluR) ligands on the induction of long-term potentiation (LTP) of field excitatory postsynaptic potentials (EPSPs) in CA1 of rat hippocampus, in particular the manner by which the nonsubtype selective mGluR ligand α-methyl-4-carboxyphenylglycine [(+)-MCPG] blocks LTP induction. Normalized control LTP was blocked by (+)-MCPG (250 μM), but not by the mGluRI selective antagonist (S)-4-carboxyphenylglycine (4-CPG), the mGluRII selective antagonist 1/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl) glycine (MCCG), or the mGluRIII antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid/α-methyl (MAP4). In contrast the mGluRII agonist {(1S,3S)-1-aminocyclopentante-1,3-dicarboxylic acid [(1S,3S)-ACPD]; 10 or 25 μM} completely and consistently blocked LTP. The block of LTP by both (1S,3S)-ACPD and (+)-MCPG could be prevented by preincubation with the mGluRII antagonist MCCG. These studies demonstrate that (+)-MCPG blocks LTP induction through an agonist action at an mGluRII receptor and not through a nonselective antagonist action.