The quinoxalinediones DNQX, CNQX and two related congeners suppress hair cell-to-auditory nerve transmission

Abstract

We tested 6,7-dinitroquinoxaline-2,3-dione (DNQX); 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQC); and 3-hydroxy-2-quinoxalinecarboxylic acid (3HQC), new kainate and quisqualate receptor antagonists, upon cochlear potentials in guinea pig. Perilymph spaces of guinea pig cochleae were perfused with artificial perilymph solutions containing up to 1000 μM concentrations of DHQC and 3HQC and 500 μM concentrations of DNQX and CNQX, at a rate of 2.5 μ1/min for 10 min. Cochlear potentials evoked by 10 kHz tone bursts of varying intensity were recorded from the basal turn scala vestibuli. Cochlear perfusion of the four drugs resulted in a dose-related suppression of the compound action potential of the auditory nerve (CAP; N 1P 1), a prolongation of N 1 latency at suprathreshold levels, an elevated CAP threshold and a decreased N 1 latency at CAP threshold. None of the drugs had significant effects on cochlear microphonics (CM) or the summating potential (SP). EC 50 values (concentrations causing a 50% reduction in CAP amplitude at 68 dB SPL) were 8 μM for DNQX, 30 μM for DHQC, 35 μM for CNQX and 1 mM for 3HQC. Results support the hypothesis that kainate and quisqualate receptors are involved in neurotransmission between the hair cell and afferent nerve.