Cochlear NMDA receptors and tinnitus

Abstract

Large dosage of aspirin produces reversible hearing loss and tinnitus. These effects have been attributed to the salicylate ion, the active component of aspirin. Salicylate acts as a competitive antagonist at the anion‐binding site of prestin, the motor protein of sensory outer hair cells. This provides an explanation for the hearing loss induced by aspirin. However, the molecular mechanism of salicylate‐induced tinnitus remains obscure. One physiological basis of salicylate ototoxicity probably originates from altered arachidonic acid metabolism. Arachidonic acid potentiates NMDA receptor currents. We therefore tested the involvement of cochlear NMDA receptors in the occurrence of tinnitus. Tinnitus was assessed with a behavioural test based on an active avoidance paradigm. Results showed that the occurrence of tinnitus induced by salicylate can be suppressed by application of NMDA antagonists into the cochlear fluids. To determine if the activation of NMDA receptors was linked to cyclooxygenase inhibition, we investigated the effect of mefenamate (a potent cyclooxygenase inhibitor). Since NMDA antagonists also blocked mefenamate‐induced tinnitus, we propose that salicylate‐induced tinnitus is mediated by cochlear NMDA receptors through an inhibition of cyclooxygenase activity. Thus target cochlear NMDA receptors may present a therapeutic strategy for treatment of tinnitus.

• salicylate
• tinnitus
• NMDA receptor
• arachidonic acid
• cyclooxygenase
• cochlea