Evidence of Tinnitus Development Due to Stress: An Experimental Study in Rats

Abstract

Objectives/Hypothesis: Tinnitus can develop due to, or be aggravated by, stress in a rat model. To investigate stress as a possible causal factor in the development of tinnitus, we designed an animal study that included tinnitus behavior and excitatory/inhibitory neurotransmitter expression after noise exposure as well as restraint stress.Study Design: An experimental animal study. Methods: Wistar rats were grouped according to single or double exposure to noise and restraint stress. The noise exposure (NE) group was subjected to 110 dB sound pressure level (SPL) of 16 kHz narrow-band noise (NBN) for 1 hour, and the restraint stress (RS) group was restrained for 1 hour with or without noise exposure. Gap prepulse inhibition of the acoustic startle (GPIAS) reflex was measured at an NBN of 16 kHz to investigate tinnitus development. Various immunohistopathologic and molecular biologic studies were undertaken to evaluate possible mechanisms of tinnitus development after noise and/or restraint stress.Results: The RS-only group showed a reduced GPIAS response, which is a reliable sign of tinnitus development. In the double-stimulus groups, more tinnitus-development signs of reduced GPIAS responses were observed. The expression of γ-aminobutyric acid A receptor α1 (GABAAR α1) in the hippocampus decreased in the NE│RS group. Increased N-methyl-Daspartate receptor1 intensities in the NE│RS group and decreased GABAAR α1 intensities in the RS and NE│RS groups were observed in the CA3 region of the hippocampus.Conclusions: Tinnitus appeared to develop after stress alone in this animal study. An imbalance in excitatory and inhibitory neurotransmitters in the hippocampus may be related to the development of tinnitus after acute NE and/or stress.

The association between stress, emotional states, and tinnitus: a mini-review

“…Though these findings do not directly correlate with tinnitus, the association with hearing loss and interaction with the auditory cortex, respectively, suggests an underlying mechanism with tinnitus onset. An experimental study evaluating whether tinnitus can develop due to, or be aggravated by stress, in rats, found reduced gap prepulse inhibition of the acoustic startle (GPIAS) reflex, a reliable indicator of tinnitus development in animals ( Kim et al, 2021 ). The study also reported decreased immunofluorescence expression of GABA A receptor α1 and increased NMDA receptor 1 immunofluorescence expression in the hippocampus in the group exposed to both noise and stress.…”

“…The study also reported decreased immunofluorescence expression of GABA A receptor α1 and increased NMDA receptor 1 immunofluorescence expression in the hippocampus in the group exposed to both noise and stress. This suggests an imbalance in excitatory and inhibitory neurotransmitters in the hippocampus to be the mechanism responsible ( Kim et al, 2021 ). The inferior colliculus is also affected by stress where atrophy of the inferior colliculus in rat brains was reported by a study assessing the effect of chronic immobilization stress isolation in the auditory and visual regions ( Dagnino-Subiabre et al, 2005 ).…”

Photobiomodulation therapy in improvement of harmful neural plasticity in sodium salicylate-induced tinnitus

“…This method is much faster, allows to separate tinnitus-positive from tinnitus-negative animals and can also be used by scientists with little experience in animal behavior [53]. At the moment, despite some limitations, several studies have used the GPIAS test and have led to significant findings in tinnitus research [54][55][56].…”