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 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.
Chen
G D
GD
University of Oklahoma, Health Sciences Center, College of Pharmacy, Oklahoma City 73190, USA. guangdi-chen@ouhsc.edu
Kong
J
J
Reinhard
K
K
Fechter
L D
LD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002248:Carbon Monoxide / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000737:chemistry / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006317:Hearing Loss, Noise-Induced / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002248:Carbon Monoxide