(-MCPG BLOCKS INDUCTION OF LTP IN CA1 OF RAT HIPPOCAMPUS VIA AGONIST ACTION AT AN MGLUR GROUP-II RECEPTOR())

We investigated the effect of metabotropic glutamate receptor (mGluR) Ligands on the induction of long-term potentiation (LTP) of field exci tatory postsynaptic potentials (EPSPs) in CA1 of rat hippocampus, in p articular the manner by which the nonsubtype selective mGluR ligand al pha-methyl-4-carboxyphenyl-glycine [(+)-MCPG] blocks LTP induction. No rmalized control LTP was blocked by (+)-MCPG (250 mu M), but not by th e mGluRI selective antagonist (S)-4-carboxyphenylglycine (4-CPG), the mGluRII selective antagonist 1/(2S,3S,4S)-2-methyl-2-(carboxycycloprop yl) glycine (MCCG), or the mGluRIII antagonist (S)-2-amino-2-methyl-4- phosphonobutanoic acid/alpha-methyl (MAP4). In contrast the mGluRII ag onist {(1S,3S)-1-aminocyclopentante-1,3-dicarboxylic acid [(1S,3S)-ACP D]; 10 or 25 mu M} completely and consistently blocked LTP. The block of LTP by both (1S,3S)-ACPD and (+)-MCPG could be prevented by preincu bation with the mGluRII antagonist MCCG. These studies demonstrate tha t (+)-MCPG blocks LTP induction through an agonist action at an mGluRI I receptor and not through a nonselective antagonist action.