High potency of the orally-active NMDA-receptor antagonist CGP 40 116 in inhibiting excitatory postsynaptic potentials of rat basolateral amygdala neurones in vitro

Barbara Ferry, Pierre Magistretti, Etienne Pralong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Conventional intracellular recordings were used to monitor postsynaptic potentials of basolateral amygdala neurones (BLA) in brain slices comprising the BLA, the entorhinal cortex (EC) and the hippocnmpus, in which the EC-BLA connections were preserved. Stimulation of the BLA with a bipolar electrode elicited complex postsynaptic potentials consisting of α-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA) receptor-mediated fast excitatory postsynaptic potentials (fast EPSPs), γ-amino-butyric acid (GABA(A)) receptor-mediated fast inhibitory postsynaptic potentials (fast IPSPs) and GABA(B) receptor-mediated slow IPSPs. Bath application of 10 μM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and of 10 μM of the GABA(A) receptor antagonist bicuculline methiodide (BMI) revealed a N-methyl-D-aspartate (NMDA) receptor-mediated slow EPSPs, which was occasionally followed by a GABA(B) receptor-mediated slow IPSPs. Under these conditions, the log concentration-response curve for D-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 40 116), a newly developed drug with proposed NMDA-receptor antagonist properties, was compared to that obtained with the 'classic' antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) in inhibiting the NMDA-mediated postsynaptic potentials. CGP 40 116 (IC50: 130 nM) was over 30 times more potent than D-AP5 (IC50: 4100 nM) in reducing NMDA-mediated slow EPSP. In conclusion, the present study indicates that CGP 40 116, a new orally-active NMDA antagonist, shows a very high potency on NMDA receptors in the amygdala and may therefore be a valuable tool for studying the behavioural effect of NMDA-receptor mediated transmission in this structure.

Original languageEnglish (US)
Pages (from-to)1555-1559
Number of pages5
JournalNeuropharmacology
Volume36
Issue number11-12
DOIs
StatePublished - Jan 1 1997

Keywords

  • Basolateral amygdala
  • CGP 40116
  • Synaptic transmission

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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