ONSET OF OTOTOXICITY IN THE CAT IS RELATED TO ONSET OF AUDITORY FUNCTION

Cats are altricial mammals; they are born deaf and undergo rapid matur ation of the auditory periphery late in the first and throughout the 2 nd week of life. Previous studies, using multiple aminoglycoside admin istration over several days or weeks, have indicated that there is a r eduction in the degree of ototoxicity in young animals provided the dr ug is administered prior to the onset of auditory function. In order t o provide a more precise relationship between the degree of ototoxicit y and auditory development, we used a single administration of Kanamyc in (KA) and the loop diuretic ethacrynic acid (EA), as the co-administ ration of these drugs is known to produce a rapid and profound hearing loss in adult animals. Thirty kittens were administered with KA and E A at ages that varied from 2 to 16 days after birth (DAB) using a fixe d dose per kilogram body weight sufficient to profoundly deafen adult animals. All animals made an uneventful recovery from the procedure. A t 26 DAB, tone-pip-evoked auditory brainstem responses (ABR) were reco rded from each animal in order to establish the extent of the hearing loss, The degree of hearing loss was compared with normal ABR audiogra ms recorded from 6 age-matched control animals. All animals treated wi th KA/EA at 9 DAB or older had a profound hearing loss similar to adul t animals. Animals treated between 2 and 8 DAB exhibited severe high-f requency hearing losses. The extent of the loss was correlated with ag e (r = 0.63) and body weight (r = 0.72) such that hearing loss tended to spread towards lower frequencies as age and/or weight increased. Al l animals exhibited bilaterally symmetrical hearing losses which remai ned relatively stable over monitoring periods of up to 6 months follow ing the drug treatment. These findings imply that the onset of ototoxi city is related, at least in part, to the onset of auditory function i n the kitten, The rapid onset of deafness following this procedure mak es it a useful technique in the study of both ototoxicity and cochlear development.