Abstract
Tinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus.
Highlights
In contrast to the chronic effect of the long-term application of salicylate, DPOAEs14 and ASECA11 decreased after a single salicylate injection, with a minimum after ~2 h and a progressive recovery over ~8 h; we investigated the effects of single administration
There were no significant differences in the gap pre-pulse inhibition of acoustic startle (GPIAS) values among the other groups, indicating that the rats in the acute treatment group did not experience tinnitus (Fig. 1a,b)
These lesions can result in neuroplasticity alterations in the peripheral and central auditory systems[1,4,14]
Summary
There were no significant differences in the PPI values among the four groups at 6, 12 and 16 kHz. of otoacoustic emissions (DPOAEs)[14], which are mainly caused by increased outer hair cell (OHC) electromotility[17], enhanced the average spectrum of electrophysiological cochleoneural activity (ASECA)[11,18], and induced changes to the synaptic ultrastructure of the dorsal cochlear nucleus (DCN)[13,19]. Many studies have investigated neural activity in the central auditory pathway (e.g., AC, IC, DCN, HP) during tinnitus1–4,8,9, , there are relatively few reports about the ultrastructural alterations. Tinnitus was induced in rats via long-term salicylate administration, and tinnitus-like behaviour was confirmed using the gap pre-pulse inhibition of acoustic startle (GPIAS) and the pre-pulse inhibition (PPI) tests.
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