Neonatal glutamate impairs rat hearing.

Abstract

It is known that excessive glutamate is neurotoxic. In the central nervous system this toxicity is selective and is presumed to be mediated by postsynaptic glutamate receptors. In a series of experiments reported here, the effects of neonatal glutamate exposure on rat hearing were investigated. The results show that glutamate administered to neonatal rats is also toxic in the auditory system, producing a high frequency hearing loss which is largely peripheral in origin and dose-dependent. This effect is not due to a general toxicity based on osmolar pressure because equiosmolar concentrations of a related substance which does not excite receptors ($\alpha$-ketoglutarate) had no effect on the audiogram. The primary peripheral target appears to be the spiral ganglion. Cochlear hair cells, which are presynaptic to afferent fibers of the spiral ganglion, were spared. Glutamate antagonists (kynurenic acid and MK-801) partially blocked this toxicity, showing that the effect of glutamate alone is receptor-mediated, at least in part. MK-801 is antagonistic to receptors excited specifically by N-methyl-D-aspartate (NMDA). Because MK-801 partially blocked the glutamate effect, it appears that NMDA receptors are involved in glutamate neurotoxicity in the neonatal rat cochlea.