MK-801 PROTECTS AGAINST CARBON MONOXIDE-INDUCED HEARING-LOSS

MK-801, a glutamate receptor blocker, has been reported to protect aga inst hypoxic-ischemic neuronal degeneration. The purpose of this study was to investigate the protective effects of MK-801 on cochlear impai rment induced by carbon monoxide (CO) in the guinea pig and whether th e protection reflected systemic or local effects. Glutamate has been p roposed to be the neurotransmitter at the inner hair cell/type I spira l ganglion cell synapse. CO (35 ml/kg ip) elevated the compound action potential threshold at high frequencies (16-40 Id-It) 30 min after tr eatment. In the group pretreated with 1 mg/kg MK-801 ip there was no s ignificant elevation of compound action potential threshold 30 min aft er CO exposure, suggesting that MK-801 provided some protection at thi s dosage. In the group pretreated with 0.1 mg/kg MK-801 there was prot ection against cochlear dysfunction 15 min after CO injection, but sig nificant elevation of compound action potential threshold occurred 30 and 60 min after CO exposure. Data also indicated that 1 mM MK-801 app lied topically on the round window membrane provided protective effect s against CO hypoxia from 15 up to 60 min. This experiment suggests th at cochlear impairment induced by CO hypoxia may result from excess ex tracellular concentrations of glutamate. (C) 1995 Academic Press, Inc.