Gap Detection Methods for Assessing Salicylate-Induced Tinnitus and Hyperacusis in Rats

Turner, Jeremy G.; Parrish, Jennifer L.

doi:10.1044/1059-0889(2008/08-0006)

Cited by 96 publications

(92 citation statements)

References 48 publications

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“…The sound-gap envelope consisted of 60 dB peak (SPL) broadband noise (BBN) or filtered noise (one-third octave bandpass, 48 dB/octave roll off, Model 3988, Krohn-Hite) centered at 10, 12.5, 16, 20, and 25 kHz, calibrated at 60 dB peak SPL. PPI was measured in parallel as a hearing level control and to test for hyperacusis (Turner and Parrish, 2008). Animals with threshold elevation and/or showing hyperacusis were eliminated from the study.…”

Section: Methodsmentioning

confidence: 99%

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Sametsky

Turner

Larsen

et al. 2015

Journal of Neuroscience

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in vitro, using the following three groups of adult rats: unexposed control (Ctrl); sound exposed with behavioral evidence of tinnitus (Tin); and sound exposed with no behavioral evidence of tinnitus (Non-T). Tonic GABA A R currents were evoked using the selective agonist gaboxadol. Months after a tinnitus-inducing sound exposure, gaboxadol-evoked tonic GABA A R currents showed significant tinnitus-related increases contralateral to the sound exposure. In situ hybridization studies found increased mRNA levels for GABA A R ␦-subunits contralateral to the sound exposure. Tin rats showed significant increases in the number of spikes per burst evoked using suprathreshold-injected current steps. In summary, we found little evidence of tinnitus-related decreases in GABAergic neurotransmission. Tinnitus and chronic pain may reflect thalamocortical dysrhythmia, which results from abnormal theta-range resonant interactions between thalamus and cortex, due to neuronal hyperpolarization and the initiation of low-threshold calcium spike bursts (Walton and Llinás, 2010). In agreement with this hypothesis, we found tinnitus-related increases in tonic extrasynaptic GABA A R currents, in action potentials/evoked bursts, and in GABA A R ␦-subunit gene expression. These tinnitus-related changes in GABAergic function may be markers for tinnitus pathology in the MGB.

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Section: Methodsmentioning

confidence: 99%

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Sametsky

Turner

Larsen

et al. 2015

Journal of Neuroscience

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“…The introduction of a silent period or gap within the background noise prior to the startle stimulus can be detected by the rat and consequently reduces its acoustic startle reflex. It is believed that the presence of tinnitus with quality similar to the background noise will override the silent gap, and therefore the rat will not suppress its startle reflex (Turner and Parrish, 2008;Turner et al, 2006;Wang et al, 2009;Yang et al, 2007;Zhang et al, 2011). We used a 115-dB SPL, 50-msec noise burst to induce the acoustic startle reflex.…”

Section: Animal Subjectsmentioning

confidence: 99%

“…In this study, we characterized blast-induced tinnitus using a gap detection acoustic startle reflex behavioral paradigm, which has been used as a screening tool for tinnitus (Turner and Parrish, 2008;Turner et al, 2006;Wang et al, 2009;Yang et al, 2007;Zhang et al, 2011). Acoustic startle reflex has also been used to assess sensorimotor reactivity of a rat model of TBI (Wiley et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Blast-Induced Tinnitus and Hearing Loss in Rats: Behavioral and Imaging Assays

Mao

Pace

Pierozynski

et al. 2012

Journal of Neurotrauma

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The current study used a rat model to investigate the underlying mechanisms of blast-induced tinnitus, hearing loss, and associated traumatic brain injury (TBI). Seven rats were used to evaluate behavioral evidence of tinnitus and hearing loss, and TBI using magnetic resonance imaging following a single 10-msec blast at 14 psi or 194 dB sound pressure level (SPL). The results demonstrated that the blast exposure induced early onset of tinnitus and central hearing impairment at a broad frequency range. The induced tinnitus and central hearing impairment tended to shift towards high frequencies over time. Hearing threshold measured with auditory brainstem responses also showed an immediate elevation followed by recovery on day 14, coinciding with behaviorally-measured results. Diffusion tensor magnetic resonance imaging results demonstrated significant damage and compensatory plastic changes to certain auditory brain regions, with the majority of changes occurring in the inferior colliculus and medial geniculate body. No significant microstructural changes found in the corpus callosum indicates that the currently adopted blast exposure mainly exerts effects through the auditory pathways rather than through direct impact onto the brain parenchyma. The results showed that this animal model is appropriate for investigation of the mechanisms underlying blast-induced tinnitus, hearing loss, and related TBI. Continued investigation along these lines will help identify pathology with injury/recovery patterns, aiding development of effective treatment strategies.

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“…In this work, we performed experiments with salicylate at a concentration of 350 mg/kg based on the literature [4,39,40,41,42,43]. The mechanism of salicylate-induced tinnitus and biological changes related to it remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Natriumsalicylicum (salicylate), the active component of aspirin, is widely used for its antipyretic, analgesic and anti-inflammatory effects. It has been revealed that salicylate can induce reversible tinnitus in both humans and animals [4,5,6,7,8,9,10,11]. Therefore, salicylate is commonly utilized to induce tinnitus in animal models for studies of tinnitus, and salicylate-induced tinnitus could be detected by the conditioned suppression/avoidance procedure [11].…”

Section: Introductionmentioning

confidence: 99%

Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus

Zhang

Xue

Liu

et al. 2014

Cell Physiol Biochem

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Background: This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus. Methods: C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons. Results: The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7^th d and decreased on the 9^th and 10^th d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days. Conclusion: This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus.

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Gap Detection Methods for Assessing Salicylate-Induced Tinnitus and Hyperacusis in Rats

Cited by 96 publications

References 48 publications

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus

Blast-Induced Tinnitus and Hearing Loss in Rats: Behavioral and Imaging Assays

Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus

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