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

Laryngoscope. 2021 Oct;131(10):2332-2340. doi: 10.1002/lary.29691. Epub 2021 Jun 22.


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-d-aspartate 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.

Level of evidence: NA Laryngoscope, 131:2332-2340, 2021.

Keywords: GABA; NMDA; Tinnitus; neurotransmitters; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Acoustic Stimulation / methods
  • Animals
  • CA3 Region, Hippocampal / pathology*
  • Disease Models, Animal
  • Humans
  • Male
  • Noise / adverse effects*
  • Rats
  • Receptors, GABA-A / analysis
  • Receptors, GABA-A / metabolism
  • Receptors, N-Methyl-D-Aspartate / analysis
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Reflex, Startle
  • Stress, Psychological / complications*
  • Stress, Psychological / psychology
  • Tinnitus / diagnosis
  • Tinnitus / etiology*
  • Tinnitus / pathology
  • Tinnitus / psychology


  • Gabra1 protein, rat
  • NMDA receptor A1
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate