The effect of nimodipine on salicylate ototoxicity in the rat as revealed by the auditory evoked brain-stem response.
Experiments have been performed to investigate the ototoxic effects of sodium salicylate administration in anaesthetised rats as recorded by the auditory evoked brain-stem response (AEBR). Sodium salicylate (300 mg kg-1 i.p.) produced time-dependent increases in hearing threshold and decreases in the four principle peaks of the AEBR. Maximum responses were obtained at 4 h post-administration and were highly significant (P < 0.001). In a further series of experiments nimodipine, a calcium channel antagonist which has been suggested as a potential therapy for tinnitus, was administered at a dose of 2 mg kg-1 s.c. at the same time as sodium salicylate. This had no effect on the changes in hearing threshold. However, it did reduce the decrease in latencies of three of the four peaks of the AEBR, such that only the decrease in latency of the first peak was significantly different when compared to the pre-injection control latency (P < 0.01). We believe that these findings show specific neurophysiological correlates of salicylate ototoxicity. Since salicylate intoxication is used as the method for inducing tinnitus in animal models, the changes in the AEBR may provide an objective measure by which potential therapeutic intervention may be tested.
Kay
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Department of Biological Sciences, Manchester Metropolitan University, UK.
Davies
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WE
D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects* / Q000502:physiology; D006309:Hearing / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012459:Salicylates / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*
D012459:Salicylates; D009553:Nimodipine