Neuroprotective effects of MK-801 on auditory cortex in salicylate-induced tinnitus: involvement of neural activity, glutamate and ascorbate

Publication date: Available online 1 February 2019

Source: Hearing Research

Author(s): Shan Xiong, Yu Song, Junxiu Liu, Yali Du, Yujing Ding, Huan Wei, Kevin Bryan, Furong Ma, Lanqun Mao

Abstract

Tinnitus may cause anxiety, depression, insomnia, which impair the quality of life of millions worldwide. However, the mechanism of tinnitus remains to be understood, it has been previously hypothesized that the activation of N-methyl-D-aspartate (NMDA) receptor is involved in the tinnitus processes and blockade of the NMDA receptor is regarded as a therapeutic strategy for tinnitus treatment even if the rescue treatment is still proved invalid in some cases. To demonstrate the therapeutic effect of the NMDA receptor blocker on tinnitus, we examined here the spontaneous firing rate (SFR) and the neurochemical dynamics in the auditory cortex (AC) of rats after sodium salicylate (SS) injection, which is a widely used model for tinnitus research. We also recorded their responses to MK-801 treatment. Electrophysiological studies showed that MK-801 significantly suppresses SFR in AC of rats with SS-induced tinnitus. In addition, by using a technique that combining in vivo microdialysis with an online electrochemical system (OECS) and a high-performance liquid chromatography (HPLC), we found that the levels of both glutamate and ascorbate in AC dramatically increased after SS injection and that MK-801 administration attenuated those response. Further studies found that MK-801 given at a time point of 30 min pre- or post- injection of SS were more effective than that given at a time point of 60 min post-SS injection, indicating that the time point of MK-801 intervention has a critical impact on the therapeutic effect. These findings suggest that MK-801 plays a neuroprotective role against hyperactivity during tinnitus induced by SS and that the therapeutic effect depends on the time point of MK-801 intervention, which would advance the studies on understanding of the therapeutic potential of NMDA receptor antagonist in tinnitus therapy.

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