Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex

Mol Pain. 2007 Apr 30:3:11. doi: 10.1186/1744-8069-3-11.

Abstract

NMDA receptors (NMDARs) are involved in excitatory synaptic transmission and plasticity associated with a variety of brain functions, from memory formation to chronic pain. Subunit-selective antagonists for NMDARs provide powerful tools to dissect NMDAR functions in neuronal activities. Recently developed antagonist for NR2A-containing receptors, NVP-AAM007, triggered debates on its selectivity and involvement of the NMDAR subunits in bi-directional synaptic plasticity. Here, we re-examined the pharmacological properties of NMDARs in the anterior cingulate cortex (ACC) using NVP-AAM007 as well as ifenprodil, a selective antagonist for NR2B-containing NMDARs. By alternating sequence of drug application and examining different concentrations of NVP-AAM007, we found that the presence of NVP-AAM007 did not significantly affect the effect of ifenprodil on NMDAR-mediated EPSCs. These results suggest that NVP-AAM007 shows great preference for NR2A subunit and could be used as a selective antagonist for NR2A-containing NMDARs in the ACC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects*
  • Excitatory Postsynaptic Potentials / physiology
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Organ Culture Techniques
  • Patch-Clamp Techniques / methods
  • Piperidines / pharmacology
  • Quinoxalines / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • 5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione
  • Excitatory Amino Acid Antagonists
  • NR2A NMDA receptor
  • NR2B NMDA receptor
  • Piperidines
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • ifenprodil