(RS)-alpha-Methyl-4-carboxyphenylglycine inhibits long-term potentiation only following the application of low frequency stimulation in the rat dentate gyrus in vitro.

The effect of the metabotropic glutamate receptor (mGluR) antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) was investigated on the induction of long-term potentiation (LTP) of alpha-amino-3-hydroxy-5- methyl-4-isoxazoleproprionate receptor-mediated excitatory postsynaptic currents (epscs) recorded from dentate granule cells in response to presynaptic stimulation of the associational/commissural pathway of the rat dentate gyrus in vitro. MCPG (500 microM, 60 min) did not inhibit the induction of LTP of epscs induced by high frequency stimulation (HFS) at sites which had received only test stimulation (0.05/s) preceding the HFS. MCPG did, however, block the induction of LTP of epscs elicited by HFS if the HFS was preceded by the induction of long-term depression elicited by low frequency stimulation (5 Hz for 3 min). After such low frequency stimulation, HFS induced only a short-term potentiation lasting up to a maximum of 10 min in the presence of MCPG.