The same neurotransmitter commonly leveraged to relieve symptoms of depression and anxiety also may exacerbate a vexing condition known as tinnitus, according to new research published in the Proceedings of the National Academy of Sciences .
Tinnitus is a constant sensation of ringing or buzzing in the ears, creating a continual irritation for some and severe anxiety for others. Global prevalence is estimated as high as 14%, with many severely affected.
Researchers with Oregon Health & Science University and Anhui University in China found in a mouse model that elevated levels of the neurotransmitter serotonin in the brain also resulted in elevated behavioral symptoms of tinnitus.
The findings should be especially meaningful for millions of people around the world who suffer from tinnitus, said co-senior author Laurence Trussell, Ph.D. , professor of otolaryngology in the OHSU School of Medicine and a scientist in the OHSU Vollum Institute and Oregon Hearing Research Center .
“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.”
Those medications include a common class of antidepressants known as selective serotonin reuptake inhibitors, or SSRIs. They alleviate symptoms of moderate to severe depression and anxiety by increasing the level of serotonin 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 started the research as a postdoctoral scholar in Trussell’s lab.
‘A delicate balance’
Researchers made significant advances from a previous study published in 2017 .
In the new study, researchers used optogenetics via fiber optics to precisely aim light into the brain such that it triggered electrical activity of neurons that produce serotonin. They then tested the behavioral response of the mice through a modified type of auditory startle response.
“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.”
The findings are consistent with the experience of people who report worsening effects of tinnitus with serotonin-elevating drugs like SSRIs, Trussell said.
“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.”
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.
All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.
Proceedings of the National Academy of Sciences
Experimental study
People
A discrete serotonergic circuit involved in the generation of tinnitus behavior
20-Apr-2026