(RS)-alpha-methyl-4-carboxyphenylglycine neither prevents induction of LTP nor antagonizes metabotropic glutamate receptors in CA1 hippocampal neurons.
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.
Chinestra
P
P
Institut National de la Santé et de la Recherche Médicale U-29, Hôpital de Port-Royal, Paris, France.
Aniksztejn
L
L
Diabira
D
D
Ben-Ari
Y
Y
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000145:classification; D009435:Synaptic Transmission / Q000187:drug effects*
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; D005998:Glycine