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J Neurophysiol 79: 1270-1276, 1998;
0022-3077/98 $5.00
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The Journal of Neurophysiology Vol. 79 No. 3 March 1998, pp. 1270-1276
Copyright ©1998 The American Physiological Society

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

N. A. Breakwell1, M. J. Rowan2, and R. Anwyl1

1 Department of Physiology and 2 Department of Pharmacology and Therapeutics, Trinity College, University of Dublin, Dublin 2, Ireland

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 alpha -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/alpha -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.




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