(RS)-alpha-methyl-4-carboxyphenylglycine neither prevents induction of LTP nor antagonizes metabotropic glutamate receptors in CA1 hippocampal neurons

Abstract

1. The effects of the putative antagonist of metabotropic glutamate receptors (mGluR), (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), were investigated in CA1 hippocampal neurons using intracellular and extracellular recordings. 2. MCPG (0.5 mM) did not antagonize the characteristic block of the slow afterhyperpolarization and spike accomodation produced by the selective mGluR agonist, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (30 microM). 3. MCPG (0.5 mM) did not prevent the inward current produced by 1S,3R-ACPD (30 microM) [240 +/- 14 and 255 +/- 21 pA (mean +/- SD) in the absence and in presence of MCPG, respectively]. 4. MCPG (0.5 mM, 10 min) did not prevent the presynaptically mediated reduction by 1S,3R-ACPD (50 microM, 10 min) of the field excitatory postsynaptic potential (EPSP) (51 +/- 7 and 64 +/- 10% in the absence and in presence of MCPG, respectively). 5. MCPG (0.5 mM) did not prevent the induction of long-term potentiation by a high-frequency tetanic stimulation of Schaffer collaterals (100 Hz, 1 s) (+61 +/- 5 and +67 +/- 16% increase in the absence and presence of MCPG, respectively). 6. These observations suggest that MCPG is not an antagonist of the subtypes of mGlu receptors that are present in CA1 pyramidal neuron. Possible selectivity of this compound for specific mGluRs is discussed in view of the regional distribution of metabotropic receptors in the hippocampus.

Increasing age reduces expression of long-term depression and dynamic range of transmission plasticity in CA1 field of the rat hippocampus

“…The GABA B and adenosine A 1 receptor-induced presynaptic inhibition of EPSPs is of a rapid onset and fully reversible within 5-10 min after agonist application. 22,57 The depression of the fEPSPs produced by activation of the presynaptic metabotropic glutamate receptor, however, lasts more than 15 min after the termination of agonist application, 5,10,35 which is comparable to that elicited by LFS (see Fig. 2 for comparison).…”

Evidence for a role for the group I metabotropic glutamate receptor in the inhibitory effect of tumor necrosis factor-α on long-term potentiation

“…This has previously been reported by some groups (Bashir et al, 1993;Bortolotto et al, 1995;Richter-Levin et al, 1994;Riedel et al, 1995), and not by others (Chinestra et al, 1993;Manzoni et al, 1994;Selig et al, 1995). Also work from mGluR5 knockout mice have shown that NMDA-receptor mediated LTP is impaired in these animals (Jia et al, 1998;Lu et al, 1997).…”

“…The involvement of the mGluRs in hippocampal LTD has been well established (Bolshakov and Siegelbaum, 1994;Fitzjohn et al, 1999;O'Mara et al, 1995;Snyder et al, 2001), however their contribution to LTP has been a subject of unresolved debate (Bashir et al, 1993;Bortolotto et al, 1995;Chinestra et al, 1993;Manzoni et al, 1994;Richter-Levin et al, 1994;Riedel et al, 1995;Selig et al, 1995). To date, eight mGluR subtypes, designated mGluR1 to mGluR8, have been cloned from the mammalian brain.…”

Direct effects of metabotropic glutamate receptor compounds on native and recombinant N -methyl- d -aspartate receptors

“…Several studies have shown that the mGluR antagonist, MCPG, can block high frequency stimulation-induced long-term potentiation at the Schaffer collateral-CA1 synapse (7,(26)(27)(28)(29)(30). Several other groups have reported that they cannot block long-term potentiation under apparently identical conditions (31)(32)(33)(34)(35). The lack of truly selective pharmacology of these mGluR compounds could in part help explain problems in using these drugs to study synaptic plasticity.…”