Glutamate neurotoxicity in the developing rat cochlea is antagonized by kynurenic acid and MK-801.
Glutamate (Glu) is neurotoxic in the neonatal rat cochlea, producing hearing impairment which is largely due to the death of spiral ganglion cells, whereas the receptor hair cells are spared. Dendritic processes of the spiral ganglion are postsynaptic to the primary afferent synapse of the auditory system. The experiments reported here were designed to test whether this apparent excitotoxicity can be blocked by Glu antagonists. The broad-spectrum antagonist kynurenic acid (KYNA) was coadministered with Glu initially to determine whether the high-frequency hearing deficit caused by Glu may be mediated by excitatory amino acid receptors. Subsequently, the N-methyl-D-aspartate (NMDA)-specific receptor blocker MK-801 was used to test whether NMDA receptors may be involved in the effect. Both antagonists partially blocked the high-frequency hearing impairment caused by Glu. The blocker-alone control groups exhibited mid-frequency effects of unknown origin. The significant antagonism of Glu-induced impairment is consistent with the hypothesis that Glu or a similar excitatory amino acid is an important afferent transmitter in the cochlea.
Janssen
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Neurotoxicology Division MD 74B, US Environmental Protection Agency, Research Triangle Park, NC 27711.
D000818:Animals; D000831:Animals, Newborn; D001299:Audiometry; D003051:Cochlea / Q000187:drug effects* / Q000254:growth & development; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid