Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats

• Published in: Neuroscience letters 1999-04, Vol.265 (2), p.71-74
• Main Authors: BASILE, A. S, BRICHTA, A. M, HARRIS, B. D, MORSE, D, COLING, D, SKOLNICK, P
• Format: Article
• Language: English
• Subjects: aminoglycoside antibiotics; aminoglycosides; Animals; Anti-Bacterial Agents - antagonists & inhibitors; Anti-Bacterial Agents - pharmacology; Biological and medical sciences; Dizocilpine Maleate - pharmacology; Drug toxicity and drugs side effects treatment; Excitatory Amino Acid Antagonists - pharmacology; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - ultrastructure; Male; Medical sciences; Microscopy, Electron, Scanning; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Streptomycin - antagonists & inhibitors; Streptomycin - poisoning; Toxicity: respiratory system, ent, stomatology; Vestibule, Labyrinth - drug effects; Vestibule, Labyrinth - ultrastructure
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00050-6

NMDA receptor mediated excitotoxicity contributes substantially to aminoglycoside antibiotic-induced cochlear damage. Since vestibular as well as cochlear hair cells have glutamatergic synapses, aminoglycoside-induced vestibulotoxicity may also have an excitotoxic component. This hypothesis was tested by examining the effects of the uncompetitive NMDA receptor antagonist dizocilpine on streptomycin-induced vestibulotoxicity. Streptomycin-treated rats exhibited almost complete destruction of sensory hair cells in the crista ampullaris, vestibular impairment in the drop test, and hyperkinesia. Concurrent treatment with dizocilpine not only rescued a substantial population of sensory hair cells in the cristae, but prevented the attendant hyperkinesis and vestibular impairments. These results indicate that excitotoxic mechanisms contribute to aminoglycoside-induced vestibulotoxicity and that NMDA antagonists may be useful in attenuating aminoglycoside ototoxicity.