Comparison of the effects of low and high concentrations of group I metabotropic receptor agonists on field potentials in the hippocampal CA1 region in vitro.
We compared the effects of low and high concentrations of the selective group I metabotropic glutamate receptor (mGluR) agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) and the nonselective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) on extracellularly recorded potentials which were evoked in the rat hippocampal CA1 region by stimulation of the Schaffer collateral/commissural pathway and on intracellularly recorded electrophysiological properties of CA1 neurons, in vitro. At low concentrations (2.5 and 5 microM) DHPG and (1S,3R)-ACPD increased while at high concentrations (20 and 50 microM) they decreased population spike amplitudes. Simultaneous recordings of population spikes in the CA1 cell layer and field excitatory postsynaptic potentials (fEPSPs) in stratum radiatum of the CA1 area revealed that the enhancement of the population spike amplitude is not associated with any change in the fEPSP slope, but the decrease in population spikes is accompanied with a decrease in the fEPSP slope, suggesting that at high concentrations both agents may attenuate excitatory synaptic transmission in CA1 cells. DHPG and (1S,3R)-ACPD had a number of direct excitatory effects on CA1 pyramidal cells like a concentration-dependent depolarization and an inhibition of the slow afterhyperpolarization, which in all probability underlay the increase in the amplitude of population spikes. At high concentrations, both mGluR agonists strongly depolarized CA1 cells indicating that depolarization block of cell discharges may underlay the reduction in the population spike amplitude. Furthermore, robust cell discharges induced by the strong depolarizations, activate several secondary processes which may significantly contribute to the action of high concentrations of DHPG and (1S,3R)-ACPD. Therefore, the effects of low and high concentrations of the studied mGluR agonists may involve different mechanisms, at low concentrations the effects can be directly related to the activation of postsynaptically localized group I mGluRs while at higher concentrations the contribution of indirect effects may predominate.
Zahorodna
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Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Pałucha
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Bijak
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D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012118:Resorcinols / Q000494:pharmacology*
D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine