The glucocorticoid antagonist mifepristone attenuates sound-induced long-term deficits in auditory nerve response and central auditory processing in female rats

Systemic corticosteroids have been themainstay of treatment for various hearing disorders formore than 30 yr. Accordingly, numerous studies have described glucocorticoids (GCs) and stressors to be protective in the auditory organ againstdamage associatedwith a variety ofhealth conditions, including noise exposure. Conversely, stressors are alsopredictive risk factors for hearing disorders.Howboth of these contrasting stress actions are linked has remained elusive.Here,wedemonstrate thathigher corticosterone levels during acoustic traumainfemale rats is highly correlated with a decline of auditory fiber responses in high-frequency cochlear regions, and that hearing thresholds and the outer hair cell functions (distortion products of otoacoustic emissions) are left unaffected. Moreover,whenGC receptor (GR) ormineralocorticoid receptor (MR) activationwas antagonized bymifepristone or spironolactone, respectively, GR, but not MR, inhibition significantly and permanently attenuated traumainduced effects on auditory fiber responses, including inner hair cell ribbon loss and related reductions of early and late auditory brainstemresponses.These findings strongly imply thathigher corticosterone stress levels profoundly impair auditory nerve processing, which may influence central auditory acuity. These changes are likely GR mediated as they are prevented by mifepristone.