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Related Experiment Video

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Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
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The glutamate receptor antagonists CNQX and MPEP decrease fast ripple events in rats treated with kainic acid.

Laura Medina-Ceja1, Carla García-Barba1

  • 1Laboratory of Neurophysiology, Department of Cellular and Molecular Biology, CUCBA, University of Guadalajara, Jalisco, Mexico.

Neuroscience Letters
|July 5, 2017
PubMed
Summary

Antagonists of glutamate receptors, CNQX and MPEP, transiently reduced fast ripples (FR) in epilepsy models. This suggests targeting AMPA/KA and mGluR5 receptors may decrease FR activity, warranting further investigation.

Keywords:
CNQXFast ripplesHippocampusKainic acidMPEPStatus epilepticus

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Area of Science:

  • Neuroscience
  • Epileptology
  • Pharmacology

Background:

  • Fast ripples (FR) are high-frequency oscillations (250-600Hz) linked to epilepsy.
  • FR are hypothesized to originate from pathologically interconnected glutamate pyramidal cells in the hippocampus.
  • Glutamate neurotransmission involves α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainite (AMPA/KA) and metabotropic mGluR5 receptors.

Purpose of the Study:

  • To investigate the effect of glutamate receptor antagonists on FR activity.
  • To test the hypothesis that blocking AMPA/KA and mGluR5 receptors decreases FR generation.

Main Methods:

  • Status epilepticus was induced using kainic acid in a rat model.
  • Intracranial EEG recordings were used to detect and evaluate FR 15 days post-induction.
  • The AMPA/KA antagonist CNQX and mGluR5 antagonist MPEP were administered intraperitoneally.

Main Results:

  • Both CNQX and MPEP significantly decreased the number of FR in the first hour post-administration (p=0.0125 and p=0.0132, respectively).
  • FR activity returned to baseline levels by the third hour after drug administration.
  • No significant differences were observed in the number of oscillations per event, frequency, or duration of FR.

Conclusions:

  • Blockade of AMPA/KA and mGluR5 receptors provides a transient decrease in FR generation.
  • These findings suggest a potential therapeutic avenue for reducing FR activity in epilepsy.
  • Further research is needed to elucidate the precise mechanisms underlying this transient effect.