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

Abstract

While a clear role has been proposed for glutamate as a putative neurotransmitter at the inner hair cell type I spiral ganglion cell synapse, the possible role of excessive glutamate release in cochlear impairment and of NMDA receptors in such a process is uncertain. The present study compares the protective effects of (+)-MK-801, an NMDA receptor antagonist, and the relatively inactive isomer (-)-MK-801 against permanent noise-induced hearing loss (NIHL). The study also asks whether (+)-MK-801 can protect against the NIHL 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 saline. Other groups of animals were exposed to the combination of noise and CO (1200 ppm) after receiving (+)-MK-801 or saline. Additional subjects received (+)-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 CAP threshold elevation induced by 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 receptor stimulation may play a role in NIHL resulting from fairly mild noise exposure. The data do not support a role for NMDA receptor stimulation in the potentiation of NIHL that results from simultaneous exposure to CO and noise.

• Authors: G D Chen, J Kong, K Reinhard, L D Fechter
• Journal: Hearing research (Hear Res) Vol. 154 Issue 1-2 Pg. 108-15 (Apr 2001) ISSN: 0378-5955 [Print] Netherlands
• PMID: 11423221 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Excitatory Amino Acid Antagonists
• Receptors, N-Methyl-D-Aspartate
• Dizocilpine Maleate
• Carbon Monoxide

Topics

• Action Potentials (drug effects)
• Animals
• Auditory Threshold (drug effects)
• Carbon Monoxide (toxicity)
• Dizocilpine Maleate (chemistry, pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Hearing Loss, Noise-Induced (etiology, physiopathology, prevention & control)
• Male
• Rats
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Stereoisomerism