Behavioral screening remains a contentious issue for animal studies of tinnitus. Most paradigms base a positive tinnitus test on an animal's natural tendency to respond to the Bsound^of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display soundconditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus Bfills in the gap.^Reliable confirmation of the behavioral indications of tinnitus can be problematic because the reinforcement contingencies of conventional discrimination tasks break down an animal's tendency to group tinnitus with sound. When responses in silence are rewarded, animals respond in silence regardless of their tinnitus status. When responses in silence are punished, animals stop responding. This study introduces stimulus classification as an alternative approach to tinnitus screening. Classification procedures train animals to respond to the common perceptual features that define a group of sounds (e.g., high pitch or narrow bandwidth). Our procedure trains animals to drink when they hear tinnitus and to suppress drinking when they hear other sounds. Animals with tinnitus are revealed by their tendency to drink in the presence of unreinforced probe sounds that share the perceptual features of the tinnitus classification. The advantages of this approach are illustrated by taking laboratory rats through a testing sequence that includes classification training, the experimental induction of tinnitus, and postinduction screening. Behavioral indications of tinnitus are interpreted and then verified by simulating a known tinnitus percept with objective sounds.

Increased prevalence of emotional distress is associated with tinnitus and hearing loss. The underlying mechanisms of the negative emotional response to tinnitus and hearing loss remain poorly understood, and it is challenging to disentangle the emotional consequences of hearing loss from those specific to tinnitus in listeners experiencing both. We addressed these questions in laboratory rats using three common rodent anxiety screening assays: elevated plus maze, open field test, and social interaction test. Open arm activity in the elevated plus maze decreased substantially after one trial in controls, indicating its limited utility for comparing pre- and post-treatment behavior. Open field exploration and social interaction behavior were consistent across multiple sessions in control animals. Individual sound-exposed and salicylate-treated rats showed a range of phenotypes in the open field, including reduced entries into the center in some subjects and reduced locomotion overall. In rats screened for tinnitus, less locomotion was associated with higher tinnitus scores. In salicylate-treated animals, locomotion was correlated with age. Sound-exposed and salicylate-treated rats also showed reduced social interaction. These results suggest that open field exploratory activity is a selective measure for identifying tinnitus distress in individual animals, whereas social interaction reflects the general effects of hearing loss. This animal model will facilitate future studies of the structural and functional changes in the brain pathways underlying emotional distress associated with hearing dysfunction, as well as development of novel interventions to ameliorate or prevent negative emotional responses.

Laboratory studies often rely on a damaging sound exposure to induce tinnitus in animal models. Because the time course and ultimate success of the induction process is not known in advance, it is not unusual to maintain sound-exposed animals for months while they are periodically assessed for behavioral indications of the disorder. To demonstrate the importance of acoustic environment during this period of behavioral screening, sound-exposed rats were tested for tinnitus while housed under quiet or constant noise conditions. More than half of the quiet-housed rats developed behavioral indications of the disorder. None of the noise-housed rats exhibited tinnitus behavior during 2 months of behavioral screening. It is widely assumed that the "phantom sound" of tinnitus reflects abnormal levels of spontaneous activity in the central auditory pathways that are triggered by cochlear injury. Our results suggest that sustained patterns of noise-driven activity may prevent the injury-induced changes in central auditory processing that lead to this hyperactive state. From the perspective of laboratory studies of tinnitus, housing sound-exposed animals in uncontrolled noise levels may significantly reduce the success of induction procedures. From a broader clinical perspective, an early intervention with sound therapy may reduce the risk of tinnitus in individuals who have experienced an acute cochlear injury.

No abstract