Supra-normal sensitivity to ototoxic antibiotic of the developing rat cochlea

Summary A period of increased sensitivity to the ototoxic antibiotic amikacin was found in the cochlea of the developing rat. Starting either at birth, 10 or 30 days of age, rats were injected i.p. daily with 200 mg/kg of amikacine for 10 days. Only in the group injected with drug from 10 to 20 days of age was there evidence of a substantial (40–100 dB) permanent threshold shift (PTS). To characterize the period of supra-normal sensitivity more precisely, independent groups of pups were injected with 50 mg/kg of amikacin from 10 to 20, 15 to 25, 20 to 30, and 30 to 40 days of age. Only those pups injeced from 10 to 20 or 15 to 25 days of age showed PTS (30–60 dB). These data, taken together with those on rat cochlear maturation indicate that the sensitive period to ototoxicity starts at the age of onset of cochlear function (around day 10) and ends a few days after the cochlea shows adult-like characteristics (3^rd postnatal week).Research supported by grants from INSERM (CRL, ARS no. 6), DGRST (BRD, DN), and CNRS (RCP 537)