In the initial proposal, it was hypothesized that an intracochlear calcium imbalance may be responsible for inducing cochlear-type tinnitus. Salicylate, and recently quinine, known to induce tinnitus systematically in humans, were used to evoke tinnitus-like sensation in animals. Since then, the following were accomplished: 1) evaluation of the time course of salicylate uptake into perilymph, CSF, and serum in albino and pigmented animals; 2) development of a behavioral paradigm based upon conditioned suppression techniques to detect and measure tinnitus in rats, and demonstration that animals did perceive tinnitus; 3) description of electrophysiological changes related to tinnitus, reflected in increased spontaneous activity of single cells recorded from the inferior colliculus after administration of sodium salicylate, compared to unchanged activity of single cells recorded from cerebellar vermis; 4) examination of the action of a calcium channel blocker on experimentally induced tinnitus, showing attenuation of salicylate induced tinnitus by the drug. Encouraged by these results confirming our animal model of tinnitus, electrophysiological and behavioral methods will be used for: 1) evaluation of electrophysiological changes induced by salicylate or quinine in the cochlea and in the activity of single cells recorded from inferior colliculus, with particular attention on characterization of recorded cells; 2) acquiring analogous results from the cochlear nuclei complex; 3) evaluation of the involvement of calcium channels with tinnitus by analyzing the effect of different calcium channel antagonists and agonists on experimentally induced tinnitus, using both behavioral and electrophysiological methods. Collectivity, data obtained during this project will not only provide a test of the hypothesis, that calcium imbalance may be responsible for inducing cochlear-type tinnitus, but will also provide insight to tinnitus based upon different mechanisms as well as the normal action of the auditory system. Finally, these results will offer information leading toward the creation of a new approach for the treatment of tinnitus and related auditory disorders.
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