CNQX increases GABA-mediated synaptic transmission in the cerebellum by anAMPA/kainate receptor-independent mechanism

GABA(A) receptor-mediated inhibitory synaptic transmission within the CNS i s often studied in the presence of glutamate receptor antagonists. However, for nearly a decade it has been known that. in the hippocampus, one of the most commonly used alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic ac id (AMPA)/kainate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dion e (CNQX), can increase the frequency of spontaneous GABA(A) receptor-mediat ed postsynaptic currents (sIPSCs). In the present study we examined the eff ect of CNQX and related compounds on GABA-mediated synaptic transmission in the cerebellum. At various stages of development, low concentrations of CN QX increased the frequency of sIPSCs recorded from granule cells. This effe ct was independent of the blocking action of CNQX on ionotropic glutamate r eceptors, as it was not observed with the broad-spectrum glutamate receptor antagonist kynurenate. No increase in sIPSC frequency was observed with th e NMDA receptor antagonists D-AP5 or 7-CIK, the selective AMPA receptor ant agonists GYKI 52466 or GYKI 53655, or the kainate receptor antagonist NS-10 2. In contrast, two other quinoxaline derivatives. NBQX and DNQX, were capa ble of increasing sIPSC frequency. These results demonstrate that the novel excitatory action of CNQX, unrelated to blockade of ionotropic glutamate r eceptors, is not restricted to the hippocampus and can be observed with str ucturally related compounds. (C) 2001 Published by Elsevier Science Ltd.