Establishment of an animal model of GPIAS-defined tinnitus-like behavior with normal auditory brainstem response threshold profiles

Noise-induced tinnitus models can include hearing loss and other auditory changes that complicate interpretation of behavioral measures. We characterized a candidate exposure paradigm associated with GPIAS-defined tinnitus-like behavior and no significant day-14 ABR threshold differences from baseline.

A normative cohort of 100 male Sprague-Dawley rats underwent repeated GPIAS testing to establish a criterion for GPIAS-defined tinnitus-like behavior. Separate cohorts were exposed bilaterally to 100-120 dB SPL white noise for 2 h and classified using the resulting 0.34 cutoff. ABR, DPOAEs, and cochlear immunofluorescence for CtBP2 presynaptic ribbons assessed auditory and morphological changes. Bilateral auditory measurements were averaged within each rat before analysis.

On day 14, ABR thresholds did not differ significantly from baseline at 100 or 105 dB SPL but remained elevated at 12 kHz after 110 dB SPL, 8 kHz after 115 dB SPL, and all six frequencies after 120 dB SPL. Findings at 105 dB SPL included persistent GPIAS-defined tinnitus-like behavior, reduced day-14 wave-I amplitude at 8 kHz, and no evident outer hair cell loss. On day 14, the tinnitus subgroup showed smaller CtBP2-positive punctum areas and fewer puncta per inner hair cell than controls and the non-tinnitus subgroup.

Bilateral exposure to 105 dB SPL white noise for 2 h provides a candidate paradigm associated with GPIAS-defined tinnitus-like behavior and auditory features consistent with hidden hearing loss, supporting further mechanistic and therapeutic studies relevant to tinnitus with normal conventional audiograms.