NMDA receptor blockage protects against permanent noise-induced hearing loss but not its potentiation by carbon monoxide

While a clear role has been proposed for glutamate as a putative neurotrans mitter at the inner hair cell type I spiral ganglion cell synapse, the poss ible role of excessive glutamate release in cochlear impairment and of NMDA receptors in such a process is uncertain. The present study compares the p rotective effects of (+)-MK-801, an NMDA receptor antagonist, and the relat ively inactive isomer (-)-MK-801 against permanent noise-induced hearing lo ss (NIHL). The study also asks whether (+)-MK-801 can protect against the N IHL potentiation by carbon monoxide (CO). Rats (n = 6) were exposed to 100- dB, 13.6-kHz octave-band noise for 2 h after receiving injection of (+)-MK- 801 hydrogen maleate (1 mg/kg), (-)-MK-801 hydrogen maleate (1 mg/kg), or s aline. Other groups of animals were exposed to the combination of noise and CO (1200 ppm) after receiving (+)-MK-801 or saline. Additional subjects re ceived (+)-MK-801. saline or CO exposure alone. Compound action potential ( CAP) threshold sensitivities were compared 4 weeks after the exposures. The results show significant protection by (+)-MK-801 against the permanent CA P threshold elevation induced bq noise alone. but no protective effect of ( -)-MK-801. (+)-MK-801 produced limited protection against threshold shifts induced by the combination of noise and CO. Outer hair cell (OHC) loss was not protected by (+)-MK-801 administration. The data suggest that NMDA rece ptor stimulation may play a role in NIHL resulting from fairly mild noise e xposure. The data do not support a role for NMDA receptor stimulation in th e potentiation of NIHL that results from simultaneous exposure to CO and no ise. (C) 2001 Elsevier Science B.V. All rights reserved.