Effect of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX) on dorsal root-, NMDA-, kainate- and quisqualate-mediated depolarization of rat motoneurones in vitro

Abstract

1. Mature in vitro rat spinal cord preparations have been used to compare the depressant effects of 6-cyano-2,3-dihydroxy-7-nitroquinoxalinedione (CNQX) and kynurenate on transmission from low threshold myelinated primary afferents in dorsal roots. EC50 values +/- s.e.mean (number of preparations in parentheses) for depression of the monosynaptic ventral root reflex were respectively 1.0 +/- 0.3 microM (5) and 135 +/- 15 microM (3) for CNQX and kynurenate. Transmission through superior cervical ganglia was not significantly affected by concentrations of CNQX up to 100 microM or kynurenate up to 5 mM. 2. Immature in vitro rat spinal cord preparations were used to measure dose-ratios for antagonism of depolarizations induced by N-methyl-D-aspartate (NMDA), kainate or quisqualate by 4, 10 and 25 microM CNQX. In the presence of 0.75 mM Mg2+ pA2 values +/- s.e.mean were respectively 4.62 +/- 0.05 (16), 5.79 +/- 0.01 (4) and 5.59 +/- 0.05 (16) for each agonist. These values were not significantly altered in the absence of added Mg2+. The mean pA2 values for kainate were significantly higher than those for quisqualate (P less than 0.01). 3. Antagonism of NMDA-induced depolarizations was evident at 10 and 25 but not 4 microM CNQX. The antagonism of NMDA was reversed by D-serine (100 and 200 microM). 4. A similarity between the relative potencies of both CNQX and kynurenate for depression of synaptic transmission and antagonism of amino acid-induced depolarizations indicates that monosynaptic transmission from myelinated primary afferents to motoneurones is mediated by kainate and/or quisqualate sub-types of non-NMDA receptors.