(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) fails to block long-term potentiation under urethane anaesthesia in vivo

S J Martin, R. G. M. Morris

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Abstract

The effects of the metabotropic glutamate receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) on the induction of long-term potentiation (LTP) in the dentate gyrus were examined under urethane anaesthesia in vivo. In experiment 1, bilateral intraventricular infusion of either 20 mM or 200 mM (R,S)-MCPG (5 microl each side) failed to block LTP in the perforant path-granule cell projection, relative to vehicle-infused controls; 30 mM D-AP5 (5 microl each side) infused in the same way as MCPG completely blocked LTP. Experiment 2, in which the contralateral perforant path-dentate gyrus pathway was used as a non-tetanized control, revealed that slight baseline changes induced by MCPG infusion were transient; again no block of LTP was obtained. The efficacy of mGluR blockade was confirmed in experiment 3, in which MCPG antagonized an increase in spontaneous activity induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). In experiment 4, significant depotentiation was induced by low frequency stimulation (5 Hz for 1 min) given 2 min after high frequency tetanization, but MCPG remained ineffective in blocking LTP after a second tetanus. In experiment 5, increasing the period of low frequency stimulation from 1 to 10 min produced greater depotentiation, but still did not unmask an MCPG-sensitive component of LTP. These experiments fail to support a role for mGluRs in the induction of LTP in the dentate gyrus under urethane anaesthesia in vivo, nor do they support the idea that a metabotropic switch controlling sensitivity to MCPG is reset by depotentiation.

Original languageEnglish
Pages (from-to)1339-54
Number of pages16
JournalNeuropharmacology
Volume36
Issue number10
DOIs
Publication statusPublished - Oct 1997

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Keywords

  • Analysis of Variance
  • Anesthesia
  • Anesthetics, Intravenous
  • Animals
  • Benzoates/pharmacology
  • Body Temperature
  • Brain/drug effects
  • Cycloleucine/analogs & derivatives
  • Drug Synergism
  • Excitatory Amino Acid Antagonists/pharmacology
  • Glycine/analogs & derivatives
  • Hippocampus/drug effects
  • Male
  • Neuroprotective Agents/pharmacology
  • Rats
  • Receptors, Metabotropic Glutamate/agonists
  • Tetanus/metabolism
  • Time Factors
  • Urethane

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