Frequency Selectivity on Aspirin-Induced Hearing Loss in Rats with Auditory Stimulus-Induced Conditioned Suppression.

Abstract

ABSTRACT. The conditioned suppression technique was employed to examine the acute effects of aspirin on auditory function in rats. Lever pressing behavior for water reinforcement was suppressed in the presence of an auditory stimulus that had been previously paired with electric shocks. A single intravenous injection of aspirin at a dose of 225 mg/kg caused an erroneous lever pressing response in the broad sound intensities of 2 kHz tone stimulus during the conditioned stimulus period. A statistically significant increase in the threshold for 2 kHz was found 1 to 72 hr after dosing but not for 4, 8 and 10 kHz. These results suggest that the hearing for low sound frequency in rats is vulnerable to the effects of aspirin. This paradigm in rats may be useful to further assess the different outer hair cells along the cochlear duct and provide an additional evidence for the aspirin ototoxicity research. -KEY WORDS: aspirin, conditioned suppression, hearing loss, low frequency, rat.J. Vet. Med. Sci. 59(10): 879-884, 1997 at the base and low frequencies at the apex [26]. Myers and Bernstein [27] reported that the hearing impairment induced by aspirin and salicylates in human does not depend on the sound frequency, but others have claimed that higher frequency is more susceptible to the effects of these drugs in human and/or guinea pigs [8,11,23]. Contrary to this, we recently reported that the hearing for lower frequency is more susceptible in the rat [22]. Most reports do agree that hearing loss and/or tinnitus are caused by aspirin; however, Boettcher and Salvi [2] reported that the results on the effects of aspirin on frequency selectivity are conflicting. To date, the ototoxicity of aspirin and/or salicylate has been assessed in guinea pigs [8,12,28], monkeys [27,30] or cats [14,15,31]. Rodents are preferable species, as the rat has an acoustic pathway similar to that of the cat and human [6,7,9], the experimental conditions for rodents are much more easily controlled and they are less expensive.If aspirin has a different effect at different OHCs along the cochlear duct, this may provide an additional approach for the aspirin ototoxicity research. In the present study of rats, to verify the results of our previous rat auditory brainstem response study [22], we first applied the conditioned suppression technique and then examined the effects of a single dose of aspirin on auditory stimulus-induced conditioned suppression, paying special attention to frequency selectivity. MATERIALS AND METHODS Animals and housing conditions:A total of 14 male Wistar SPF rats (CLEA Japan Inc., Japan) weighing 350 to 400 g were used. At the start of treatment, the animals were 20 weeks old. They were maintained on a mild waterdeprivation schedule to keep body weight at approximately 90% of the free-drinking levels throughout the pre-treatmentThe adverse effects, such as hearing loss and tinnitus, following the administration of aspirin and/or salicylates have long been known, and auditory impairment by these agents has been confirm...