Behavioral ototoxicology.

Methods for the evaluation in experimental animals of toxic substances that produce hearing impairment are described. In the experiments reported here, animals were trained by positive reinforcement operant conditioning procedures so that their hearing could be examined by behavioral means. When normal hearing was established, aminoglycosidic antibiotics (kanamycin and dihydrostreptomycin) were given daily and hearing tests administered in order that the course of hearing loss could be closely followed. Initial loss of sensitivity to the high frequencies always progressed in time to impairment at the low frequencies, and these changes in hearing were correlated with a loss of receptor cells in the inner ear which started in the basal region of the cochlea and advanced toward the apex. Although such behavioral procedures are moderately expensive to instrument and relatively time-consuming to apply, they are shown to yield valid quantitative measures of hearing. Further, they provide for reliable early detection of the toxic process and a measure of behavioral impairment that can be precisely related to the histopathological changes that occur simultaneously in the inner ear and auditory nerve.