CNQX BLOCKS ACIDIC AMINO-ACID INDUCED DEPOLARIZATIONS AND SYNAPTIC COMPONENTS MEDIATED BY NON-NMDA RECEPTORS IN RAT HIPPOCAMPAL SLICES

6-Cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX; FG 9065) is a newly excitatory amino acid antgonist. In the spinal cord it has been reported to selectively block responses to acidic amino acids acting at receptors of the non-N-methyl-D-aspartate (non-NMDA) type. Here we report that in the rat hippocampal slices bathed in Mg2+-free medium 10 .mu.M CNQX reversibly blocks responses to .alpha.-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), quisqualate and kainate but not NMDA. The synaptic response evoked by low frequency stimulation of Schaeffer collateral-commissural fibres in 1 mM Mg2+-containing medium is completely blocked by this concentration of CNQX. In contrast the synaptic response evoked in Mg2+-free medium is not fully blocked by CNQX. The CNQX-insensitive component is, however, abolished by addition of a selective NMDA antagonist. The use of CNQX has allowed for the first time selective synaptic activation of NMDA receptors in the hippocampus.