Abstract
Numerous behavioral paradigms have been developed to assess tinnitus-like behavior in animals. Nevertheless, they are often limited by prolonged training requirements, as well as an inability to simultaneously assess onset and lasting tinnitus behavior, tinnitus pitch or duration, or tinnitus presence without grouping data from multiple animals or testing sessions. To enhance behavioral testing of tinnitus, we developed a conditioned licking suppression paradigm to determine the pitch(s) of both onset and lasting tinnitus-like behavior within individual animals. Rats learned to lick water during broadband or narrowband noises, and to suppress licking to avoid footshocks during silence. After noise exposure, rats significantly increased licking during silent trials, suggesting onset tinnitus-like behavior. Lasting tinnitus-behavior, however, was exhibited in about half of noise-exposed rats through 7 weeks post-exposure tested. Licking activity during narrowband sound trials remained unchanged following noise exposure, while ABR hearing thresholds fully recovered and were comparable between tinnitus(+) and tinnitus(-) rats. To assess another tinnitus inducer, rats were injected with sodium salicylate. They demonstrated high pitch tinnitus-like behavior, but later recovered by 5 days post-injection. Further control studies showed that 1): sham noise-exposed rats tested with footshock did not exhibit tinnitus-like behavior, and 2): noise-exposed or sham rats tested without footshocks showed no fundamental changes in behavior compared to those tested with shocks. Together, these results demonstrate that this paradigm can efficiently test the development of noise- and salicylate-induced tinnitus behavior. The ability to assess tinnitus individually, over time, and without averaging data enables us to realistically address tinnitus in a clinically relevant way. Thus, we believe that this optimized behavioral paradigm will facilitate investigations into the mechanisms of tinnitus and development of effective treatments.
Highlights
Tinnitus, a phantom auditory perception that occurs in the absence of external acoustic stimulation, is a prevalent health condition
We sought to develop an optimized behavioral paradigm that is capable of efficiently assessing tinnitus-like behavior in animals
We set out to establish a paradigm that did not require very long training periods (i.e. 1–2 months), that could determine onset tinnitus, lasting tinnitus, and tinnitus pitch, and that could determine tinnitus in individual animals over time and without averaging data. These capabilities would enable us to realistically address tinnitus in a realistic and clinically relevant manner. We believe that such optimized behavioral testing can significantly benefit the ongoing endeavors towards delineating the mechanisms underlying tinnitus, and developing effectiveness treatments
Summary
A phantom auditory perception that occurs in the absence of external acoustic stimulation, is a prevalent health condition. It affects approximately 50 million Americans [1, 2], and can impair everyday life [3,4,5,6,7], costing an estimated 2 billion dollars for U.S veterans alone [8]. A vital step to advance progress in these two arenas is to clearly understand the underlying mechanisms of tinnitus as related to clinical diagnosis and treatment. Achieving this step requires in-depth investigations using animal models. The development of reliable paradigms for testing tinnitus-related behaviors is urgently needed
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