Isoflurane anesthesia suppresses distortion product otoacoustic emissions in rats.

A commonly used anesthetic, isoflurane, can impair auditory function in a dose-dependent manner. However, in rats, isoflurane-induced auditory impairments have only been assessed with auditory brainstem responses; a measure which is unable to distinguish if changes originate from the central or peripheral auditory system. Studies performed in other species, such as mice and guinea-pigs, suggests auditory impairment stems from disrupted OHC amplification. Despite the wide use of the rat in auditory research, these observations have yet to be replicated in the rat animal model. This study used distortion product otoacoustic emissions to assess outer hair cell function in rats that were anesthetized with either isoflurane or a ketamine/xylazine cocktail for approximately 45 min. Results indicate that isoflurane can significantly reduce DPOAE amplitudes compared to ketamine/xylazine, and that responses were more variable with isoflurane than ketamine/xylazine over the 45-min test period. Based on these observations, isoflurane should be used with caution when assessing peripheral auditory function to avoid potentially confounding effects.

Prolonged low-level noise-induced plasticity in the peripheral and central auditory system of rats.

Prolonged low-level noise exposure alters loudness perception in humans, presumably by decreasing the gain of the central auditory system. Here we test the central gain hypothesis by measuring the acute and chronic physiologic changes at the level of the cochlea and inferior colliculus (IC) after a 75-dB SPL, 10-20-kHz noise exposure for 5weeks. The compound action potential (CAP) and summating potential (SP) were used to assess the functional status of the cochlea and 16 channel electrodes were used to measure the local field potentials (LFP) and multi-unit spike discharge rates (SDR) from the IC immediately after and one-week post-exposure. Measurements obtained immediately post-exposure demonstrated a significant reduction in supra-threshold CAP amplitudes. In contrast to the periphery, sound-evoked activity in the IC was enhanced in a frequency-dependent manner consistent with models of enhanced central gain. Surprisingly, one-week post-exposure supra-threshold responses from the cochlea had not only recovered, but were significantly larger than normal, and thresholds were significantly better than controls. Moreover, sound-evoked hyperactivity in the IC was sustained within the noise exposure frequency band but suppressed at higher frequencies. When response amplitudes representing the neural output of the cochlea and IC activity at one-week post exposure were compared with control animal responses, a central attenuation phenomenon becomes evident, which may play a key role in understanding why low-level noise can sometimes ameliorate tinnitus and hyperacusis percepts.

Potassium ion channel openers, Maxipost and Retigabine, protect against peripheral salicylate ototoxicity in rats.

Sodium Salicylate (SS) reliably induces a sensorineural hearing loss and tinnitus when administered in high doses. Recent animal modeled studies indicate that potassium channel openers such as Maxipost and Retigabine (RTG) can block SS- or noise-induced tinnitus respectively; however, the origins and mechanisms are poorly understood. Since SS blocks the same potassium channels that Maxipost and RTG open, we postulated that these drugs might influence peripheral auditory function. To test this hypothesis Maxipost or RTG were administered alone or in combination with SS in rats. When administered alone, Maxipost and RTG had no effect on distortion product otoacoustic emissions (DPOAE) or compound action potentials (CAPs). However when Maxipost or RTG were administered with SS, Maxipost prevented the SS-reduced CAP amplitudes at high frequencies (≥20 kHz) and RTG prevented SS-reduced CAP amplitudes at low frequencies (≤8 kHz). These results suggest that Maxipost and RTG can protect against peripheral damage and therefore reduce the incidence of tinnitus.