A Conditioned Behavioral Paradigm for Assessing Onset and Lasting Tinnitus in Rats.

A Conditioned Behavioral Paradigm for Assessing Onset and Lasting Tinnitus in Rats.
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DOI:
10.1371/journal.pone.0166346
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Zhang J
Zhang J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pace E;Luo H;Bobian M;Panekkad A;Zhang X;Zhang H;Zhang J

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已经开发了许多行为范例来评估动物中的耳鸣样行为。然而,它们通常受到长期训练要求的限制,以及无法同时评估耳鸣发作和持续行为、耳鸣音调或持续时间或耳鸣存在,而不对来自多个动物或测试会话的数据进行分组。为了加强耳鸣的行为测试,我们开发了一种条件性舔抑制范例,以确定个体动物中发作和持续耳鸣样行为的音高。老鼠学会了在宽带或窄带噪音中舔水,并在安静时抑制舔水以避免脚震。噪声暴露后,大鼠在安静的试验中显著增加舔,表明发作耳鸣样行为。然而,通过暴露后7周的测试,在大约一半的噪声暴露大鼠中表现出持续的耳鸣行为。在噪声暴露后,窄带声音试验中的舔活动保持不变,而ABR听力阈值完全恢复,耳鸣(+)和耳鸣(-)大鼠之间相当。为了评估另一种耳鸣诱导剂,给大鼠注射水杨酸钠。它们表现出高音调耳鸣样行为,但后来在注射后5天恢复。进一步的对照研究表明:1):接受足电击测试的假噪声暴露大鼠没有表现出耳鸣样行为,2):与接受电击测试的大鼠相比,接受噪声暴露或假噪声暴露但不接受足电击测试的大鼠没有表现出根本的行为变化。总之,这些结果表明,这种模式可以有效地测试噪声和水杨酸诱导的耳鸣行为的发展。随着时间的推移,单独评估耳鸣的能力,而无需平均数据,使我们能够以临床相关的方式现实地解决耳鸣。因此,我们相信,这种优化的行为模式将有助于调查耳鸣的机制和有效治疗的发展。
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.
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