(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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

Fingerprint

alpha-methyl-4-carboxyphenylglycine
Long-Term Potentiation
Urethane
Anesthesia
Long-Term Synaptic Depression
Dentate Gyrus
Perforant Pathway
Intraventricular Infusions
Excitatory Amino Acid Antagonists
Metabotropic Glutamate Receptors
Tetanus
4-carboxyphenylglycine

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

Cite this

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title = "(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) fails to block long-term potentiation under urethane anaesthesia in vivo",
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.",
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author = "Martin, {S J} and Morris, {R. G. M.}",
year = "1997",
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doi = "10.1016/S0028-3908(97)00129-9",
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(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) fails to block long-term potentiation under urethane anaesthesia in vivo. / Martin, S J; Morris, R. G. M.

In: Neuropharmacology, Vol. 36, No. 10, 10.1997, p. 1339-54.

Research output: Contribution to journalArticle

TY - JOUR

T1 - (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) fails to block long-term potentiation under urethane anaesthesia in vivo

AU - Martin, S J

AU - Morris, R. G. M.

PY - 1997/10

Y1 - 1997/10

N2 - 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.

AB - 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.

KW - Analysis of Variance

KW - Anesthesia

KW - Anesthetics, Intravenous

KW - Animals

KW - Benzoates/pharmacology

KW - Body Temperature

KW - Brain/drug effects

KW - Cycloleucine/analogs & derivatives

KW - Drug Synergism

KW - Excitatory Amino Acid Antagonists/pharmacology

KW - Glycine/analogs & derivatives

KW - Hippocampus/drug effects

KW - Male

KW - Neuroprotective Agents/pharmacology

KW - Rats

KW - Receptors, Metabotropic Glutamate/agonists

KW - Tetanus/metabolism

KW - Time Factors

KW - Urethane

U2 - 10.1016/S0028-3908(97)00129-9

DO - 10.1016/S0028-3908(97)00129-9

M3 - Article

VL - 36

SP - 1339

EP - 1354

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 10

ER -