Dose-dependent changes in the rat cochlea following aminoglycoside intoxication. I. Physiological study

The dose-dependent effects of amikacin on the rat cochlea were studied electrophysiologically using CAP audiograms, amplitude and latency-intensity curves, and CAP tuning curves using a forward masking procedure. The animals were given a daily subcutaneous injection of amikacin in doses ranging from 100 to 1000 mg/kg, for five consecutive days, and were tested one month after the end of the treatment. No functional evidence of ototoxicity was found in animals treated with 100 and 200 mg/kg per day doses of amikacin. The first electrophysiological changes were observed with doses of 300-600 mg/kg per day. They consisted of a broadening of the tip and a hypersensitivity of the tail of the CAP tuning curves, without a change in the CAP threshold sensitivity and latency. Animals treated with 700 mg of amikacin showed an elevation of the tip of the CAP tuning curves and an increase in CAP latency. The classical feature of antibiotic ototoxicity was observed in animals given 800 mg/kg per day of amikacin with an increase in CAP threshold sensitivity and latency, a disruption of the CAP amplitude-intensity function, and a clear hyposensitivity of the CAP tuning curves. These results are discussed in the light of anatomical findings described in a companion paper.