A Conditioned Behavioral Paradigm for Assessing Onset and Lasting Tinnitus in Rats.
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.
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, 4201 Saint Antoine, Detroit, Michigan 48201, United States of America.
Edward
E
Pace
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, 4201 Saint Antoine, Detroit, Michigan 48201, United States of America.
Hao
H
Luo
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, 4201 Saint Antoine, Detroit, Michigan 48201, United States of America.
Michael
M
Bobian
Department of Electrical Engineering, Wayne State College of Engineering, 5050 Anthony Wayne Drive, Detroit, Michigan 48202, United States of America.
Ajay
A
Panekkad
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, 4201 Saint Antoine, Detroit, Michigan 48201, United States of America.
Xueguo
X
Zhang
Department of Biological Sciences, University of Windsor, 401 Sunset Avenue, Windsor, Ontario, Canada.
Huiming
H
Zhang
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, 4201 Saint Antoine, Detroit, Michigan 48201, United States of America.|Department of Communication Sciences & Disorders, Wayne State University College of Liberal Arts & Sciences, 60 Farnsworth St., Detroit, Michigan 48202, United States of America.
Jinsheng
J
Zhang
D000161:Acoustic Stimulation; D000818:Animals; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D004597:Electroshock; D006120:Grooming / Q000502:physiology*; D008297:Male; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012980:Sodium Salicylate / Q000009:adverse effects*; D013016:Sound; D014012:Tinnitus / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology
D012980:Sodium Salicylate