Novel Animal Model of Tinnitus, New Grant, Propel UB Researchers Forward in Search for Tinnitus Treatment
A novel rat behavioral model of tinnitus that will allow researchers to study this debilitating condition in a manner never before possible and to test potential treatments has been developed by researchers with the University at Buffalos Center for Hearing & Deafness.
Center researchers, who have been studying tinnitus for more than a decade, will use this animal model to monitor the activity of individual neurons in the animals brains where the phantom sounds of tinnitus are thought to occur in a new study funded by a $167,000 grant from the American Tinnitus Association.
The novel behavior paradigm, which involved training the animals to abstain from drinking when they perceive sound, is described in the April issue of Hearing Research.
"Having this animal model to work with and to observe will allow us to make significant strides in identifying the underlying neural mechanisms of this condition," said Richard Salvi, Ph.D., director of the Center for Hearing & Deafness and primary researcher on the new study. "We hope this research will bring us closer to finding a treatment for tinnitus and to providing relief to the millions who suffer from it.
"The neural mechanisms that give rise to the phantom sound of tinnitus are not well understood because of the limited number of animal models available to work with," continued Salvi, professor in the Department of Communicative Disorders and Sciences in the UB College of Arts and Sciences. "This new model gives us the ability to have an animal make a behavioral response to tell us it hears the phantom sound of tinnitus and to measure what is going on in the brain at the same time. No one has been able to do this before in a behaving animal."
The model was developed by Edward Lobarinas, a doctoral student in the UB Department of Communicative Disorders and Sciences and a member of the center. The rats were trained to drink from their water dispenser during periods of quiet, but to refrain from drinking during actual noise, defined as "licks in sound."
Once this pattern was established, researchers injected each animal with saline or a solution containing increasing concentrations of sodium salicylate, or aspirin, which is known to induce the phantom sounds of tinnitus. Each dose of aspirin -- 50, 100, 150 and 350 milligrams per kilogram of body weight (mg/kg) -- was given for two days. Doses were separated by a week to allow behavior to return to baseline between treatments. Researchers hypothesized that when trained animals sensed the phantom sound of tinnitus during quiet periods, they would interpret it as "real sound" and would refuse to drink.
Results showed that when animals received saline or the 50 mg/kg aspirin solution, they drank during quiet as they were conditioned to do, indicating no evidence of tinnitus. The 100 mg/kg dose produced a slight suppression of licking during quiet. However, the 150 mg/kg and 350 mg/kg treatments almost completely suppressed licking during the quiet interval, indicating the rats were hearing a phantom sound. The high dose of sodium salicylate produced behaviors in quiet that were similar to a real sound of 40 decibels, Salvi said.
"This cessation of licking during quiet would appear to indicate the animals are sensing a phantom noise, the condition that defines tinnitus, although no noise was present," said Lobarinas. "After the salicylate treatment ended, the rats gradually returned to their normal conditioned behavior in two-to-three days, indicating the disappearance of tinnitus."
With the two-year grant from the American Tinnitus Association, the researchers will monitor and correlate changes in neural activity in the auditory cortex, a region of the brain responsible for processing and interpreting sound, by taking readings from individual neurons before, during and after inducing tinnitus.
"We expect to see that a subpopulation of neurons in the auditory cortex will increase their activity when the rats experience tinnitus and that the activity will decrease when the tinnitus disappears," said Salvi.
Additional researchers on the project to develop an animal behavioral model of tinnitus were Wei Sun, research assistant professor, and Ross Cushing, AuD, both in the UB Department of Communicative Disorders and Sciences.
Their research was supported in part by grants from the National Institute on Deafness and Other Communication Disorders and the Royal National Institute for Deaf People.
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Lois Baker | University at Buffalo