Salicylate toxicity model of tinnitus

Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs, or aging, which affects ∼14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed

Effects of neonatal deafness on resting-state functional network connectivity.

Normal brain development depends on early sensory experience. Behavioral consequences of brain maturation in the absence of sensory input early in life are well documented. For example, experiments with mature, neonatally deaf human or animal subjects have revealed improved peripheral visual motion detection and spatial localization abilities. Such supranormal behavioral abilities in the nondeprived sensory modality are evidence of compensatory plasticity occurring in deprived brain regions at some point or throughout development. Sensory deprived brain regions may simply become unused neural real-estate resulting in a loss of function. Compensatory plasticity and loss of function are likely reflected in the differences in correlations between brain networks in deaf compared with hearing subjects. To address this, we used resting-state functional magnetic resonance imaging (fMRI) in lightly anesthetized hearing and neonatally deafened cats. Group independent component analysis (ICA) was used to identify 20 spatially distinct brain networks across all animals including auditory, visual, somatosensory, cingulate, insular, cerebellar, and subcortical networks. The resulting group ICA components were back-reconstructed to individual animal brains. The maximum correlations between the time-courses associated with each spatial component were computed using functional network connectivity (FNC). While no significant differences in the delay to peak correlations were identified between hearing and deaf cats, we observed 10 (of 190) significant differences in the amplitudes of between-network correlations. Six of the significant differences involved auditory-related networks and four involved visual, cingulate, or somatosensory networks. The results are discussed in context of known behavioral, electrophysiological, and anatomical differences following neonatal deafness. Furthermore, these results identify novel targets for future investigations at the neuronal level

Comparison of salicylate- and quinine-induced tinnitus in rats: development, time course, and evaluation of audiologic correlates

BACKGROUND: Salicylate and quinine have been shown to reliably induce short-term tinnitus when administered at high doses. The present study compared salicylate and quinine-induced tinnitus in rats using the gap prepulse inhibition of acoustic startle (GPIAS). METHODS: Twenty-four rats were divided into 2 groups; the first group (n = 12) was injected with salicylate (300 mg kg -1 d -1), whereas the second (n = 12) was treated with quinine orally at a dose of 200 mg kg -1 d -1. Animals were treated daily for 4 consecutive days. All rats were tested for tinnitus and hearing loss before and 2, 24, 48, 72, and 96 hours after the first drug administration. Tinnitus was assessed using GPIAS; hearing function was measured with distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response. RESULTS: Salicylate treatment induced transient tinnitus with a pitch near 16 kHz starting 2 hours posttreatment, persisting over the 4-day treatment period and disappearing 24 hours later. Animals in the quinine group showed GPIAS changes at a higher pitch (20 kHz); however, changes were more variable among animals, and the mean data were not statistically significant. Hearing function varied across treatments. In the salicylate group, high-level DPOAEs were slightly affected; most changes occurred 2 hours posttreatment. Low-level DPOAEs were affected at all frequencies with a progressive dose-dependent effect. In the quinine group, only high-level DPOAEs were affected, mainly at 16 kHz. CONCLUSION: The present study highlights the similarities and differences in the frequency and the time course of tinnitus and hypoacusis induced by salicylate and quinine. Transient tinnitus was reliably induced pharmacologically with salicylate, whereas hearing loss remained subclinical with only minor changes in DPOAEs