Tinnitus is frequently linked with psychosocial stress in clinical observations, but whether stress alone can cause the neural changes that generate tinnitus remains unclear. This preclinical study addressed that question by isolating repeated chronic stress as the single independent variable in a well-established Mongolian gerbil model. The investigators aimed to determine if stress exposure, in the absence of acoustic trauma, is sufficient to produce behavioural signs of tinnitus or to induce loss of inner hair cell synapses (cochlear synaptopathy).
Animals were subjected to a repeated, inescapable electric foot-shock protocol over a three-week period to establish a chronic, repeated stress paradigm. The experimental approach intentionally excluded acoustic trauma so that any observed tinnitus-like behaviour or synaptic pathology could be attributed to stress exposure alone. The study combined three measurement domains to evaluate outcomes: behavioural readouts of tinnitus perception, endocrine markers of stress system activation, and histological counts of inner hair cell ribbon synapses across the cochlea.
Behavioural assessment relied on the gap-prepulse inhibition (GPI) of the acoustic startle reflex, a commonly used behavioural assay for tinnitus perception in rodents. Across the stressed and control groups, only isolated cases of behaviour consistent with tinnitus were detected. The frequency of these isolated occurrences matched what the authors interpret as the expected rate of false-positive detections for the assay. Importantly, these isolated behavioural signs were distributed evenly between stress-exposed animals and controls, providing no systematic evidence that repeated chronic stress produced tinnitus-like percepts in this model.
Endocrine activation of the stress system was evaluated through repeated measures of serum cortisol. The stress protocol reliably activated the endocrine response: researchers observed transient increases in serum cortisol following specific stress sessions. However, basal cortisol values returned to baseline after completion of the stress period, indicating that the transient endocrine responses did not produce a sustained elevation in basal cortisol when measured after the chronic stress protocol ended.
Histological analyses focused on ribbon synapse counts at inner hair cells across the cochlear frequency range to test for synaptopathy. The investigators report preserved ribbon synapse numbers throughout the cochlea in stress-exposed animals. No evidence of stress-induced cochlear synaptopathy was observed under the conditions of this study, meaning ribbon synapse counts did not differ systematically between stressed and control animals.
The study examined whether endocrine activation, behavioural signs, and synaptic counts were related on a systematic level. No consistent relationships were identified among these measures: transient cortisol increases did not map onto increased rates of tinnitus-like behaviour, nor did they predict reductions in inner hair cell ribbon synapse numbers. Behavioural occurrences interpreted as tinnitus-like were rare and occurred at rates consistent with false positives, and were not associated with reduced synapse counts.
Taken together, the results indicate that repeated chronic stress delivered as inescapable foot shocks over three weeks is sufficient to activate the endocrine stress response transiently but is not sufficient, by itself, to induce behavioural signs of tinnitus or to cause cochlear synaptopathy in Mongolian gerbils when no acoustic trauma is present. The authors interpret these findings as evidence against a primary causal role of stress alone in the generation of tinnitus. Instead, the data support models in which stress may modulate the expression, salience, or severity of tinnitus symptoms in the presence of pre-existing auditory dysfunction rather than acting as an initiating factor.
The article is presented as a preprint and has not undergone peer review. The authors declared no competing interests. The source did not report further methodological details such as sample sizes, specific timing of measurements, or statistical values in the abstract; those details were not provided in the source material summarized here.