A widely used neurotransmitter for treating mental health conditions may have unintended consequences for auditory perception.
New research published in the Proceedings of the National Academy of Sciences suggests that a neurotransmitter widely used to treat depression and anxiety may also worsen a frustrating condition known as tinnitus.
Tinnitus causes a persistent ringing or buzzing in the ears. For some people it is a minor nuisance, but for others it can lead to significant distress and anxiety. The condition is common worldwide, affecting up to 14% of the population, with many cases considered severe.
Scientists at Oregon Health & Science University and Anhui University in China used a mouse model to study the effects of serotonin in the brain. They found that higher serotonin levels were linked to stronger behavioral signs associated with tinnitus.
Co-senior author Laurence Trussell, Ph.D., a professor of otolaryngology at the OHSU School of Medicine and a researcher at the OHSU Vollum Institute and Oregon Hearing Research Center, said the results could be important for millions of people living with tinnitus.
“People with tinnitus should work with their prescribing physician to find a drug regimen that gives them a balance between relief of psychiatric symptoms like depression and anxiety, while minimizing the experience of tinnitus,” Trussell said. “This study highlights the importance of clinicians recognizing and validating patient reports of medication-associated increases in tinnitus.”
Antidepressants and Auditory Effects
The medications involved include selective serotonin reuptake inhibitors, or SSRIs, a widely used class of antidepressants. These drugs treat moderate to severe depression and anxiety by increasing serotonin levels in the brain.
“We’ve suspected that serotonin was involved in tinnitus, but we didn’t really understand how,” said co-author Zheng-Quan Tang, Ph.D., of Anhui University in China. “Now, using mice, we’ve found a specific brain circuit involving serotonin that goes straight to the auditory system, and found that it can induce tinnitus-like effects. When we turned that circuit off, we were able to ameliorate the tinnitus significantly.
“This gives us a much clearer picture of what’s going on in the brain — and points toward new possibilities for treatment.”
Tang began this work as a postdoctoral researcher in Trussell’s lab.
‘A delicate balance’
The study builds on earlier research published in 2017 and provides new details about how tinnitus may develop.
Researchers used optogenetics, a technique that uses fiber optics to deliver light into the brain, allowing them to activate serotonin-producing neurons with precision. They then measured how the mice responded using a modified auditory startle test.
“When you stimulate these serotonergic neurons, we can see that it stimulates activity in the auditory region in the brain,” Trussell said. “We also saw that animals then behaved as if they were hearing tinnitus. In other words, it’s producing symptoms that we would expect to be experienced as tinnitus in humans.”
These results match reports from some patients who notice that tinnitus worsens when taking medications that increase serotonin, including SSRIs.
“Our study suggests a delicate balance,” he said. “It may be possible to develop cell- or brain region-specific drugs that steer the elevation of serotonin in some brain regions but not others. In that way, it may be possible to separate the beneficial and important effects of the antidepressant from the potentially harmful effects on hearing.”
Reference: “A discrete serotonergic circuit involved in the generation of tinnitus behavior” by Meng-Ting Yu, Zhen-Yu Dai, Si-Xin Wang, Ke-Jian Wang, Chun-Hui Qin, Yi-Mei Zhou, Xiao-Tao Guo, Chun-Chen Pan, Jia-Qiang Sun, Jing-Wu Sun, Wei-Heng Chen, Yan Jin, Qin-Wei Wu, Laurence O. Trussell and Zheng-Quan Tang, 20 April 2026, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2509692123
Trussell’s work was supported by the National Institutes of Health, award RO1DC004450. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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