BEHAVIORAL ASSESSMENT AND IDENTIFICATION OF A MOLECULAR MARKER IN A SALICYLATE-INDUCED TINNITUS IN RATS
BEHAVIORAL ASSESSMENT AND IDENTIFICATION OF A MOLECULAR MARKER IN A SALICYLATE-INDUCED TINNITUS IN RATS
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DOI：
10.1016/j.neuroscience.2009.11.048
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发表时间：
2010-02-17
期刊：
影响因子：
3.3
通讯作者：
Inohara, H.
中科院分区：
文献类型：
--
作者：
Kizawa, K.;Kitahara, T.;Inohara, H.
耳鸣是一种不可观察的幻觉感觉。因此，这是一种难以调查的疾病，迄今为止，还没有开发出有效的治疗方法。为了接近这种幻肢感觉，我们的目的是使用水杨酸盐（阿司匹林的一种活性成分，已知可诱导耳鸣）建立大鼠耳鸣行为模型。我们还旨在建立一个耳鸣的分子标志物，通过评估瞬时受体电位阳离子通道超家族V-1（TRPV 1）在水杨酸诱导的耳鸣大鼠听觉通路的表达。训练动物执行“主动回避任务”：通过电足电击使动物在听到声音时移动到调节箱的另一侧。动物接受单次注射盐水或水杨酸盐（400 mg/kg i. p.）并且在注射后2小时测量假阳性反应作为在静默期期间的运动次数。当条件刺激为60 dB声压级（SPL）和16 kHz时，水杨酸处理动物的反应数量最多。这表明动物在注射水杨酸后2 h可感觉到耳鸣，相当于60 dB SPL和16 kHz引起的耳鸣。通过实时PCR和蛋白质印迹分析，TRPV 1表达在水杨酸注射后2小时在螺旋神经节细胞中显著上调，并且这种上调连同假阳性反应数量的增加一起被辣椒平（10 mg/kg i. p.）显著抑制，TRPV 1的特异性拮抗剂。提示水杨酸可能通过激活大鼠听觉通路中的TRPV 1而引起耳鸣。(C)2010年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Tinnitus is a non-observable phantom sensation. As such, it is a difficult condition to investigate and, to date, no effective treatment has been developed. To approach this phantom sensation, we aimed to develop a rat behavioral model of tinnitus using salicylate, an active component of aspirin known to induce tinnitus. We also aimed to establish a molecular marker of tinnitus by assessing the expression of transient receptor potential cation channel superfamily V-1 (TRPV1) in the rat auditory pathway during salicylate-induced tinnitus. Animals were trained to perform "an active avoidance task": animals were conditioned by electrical footshock to move to the other side of the conditioning box when hearing a sound. Animals received a single injection of saline or salicylate (400 mg/kg i.p.) and false positive responses were measured 2 h after injection as the number of movements during a silent period. The number of responses in salicylate-treated animals was highest when the conditioned stimulus was 60 dB sound pressure level (SPL) and 16 kHz. This indicates that animals could feel tinnitus 2 h after salicylate injection, equivalent to that induced by 60 dB SPL and 16 kHz. By means of real-time PCR and western blot analysis, TRPV1 expression was significantly upregulated in spiral ganglion cells 2 h after salicylate injection and this upregulation together with the increase in the number of false positive responses was significantly suppressed by capsazepine (10 mg/kg i.p.), a specific antagonist of TRPV1. This suggests that salicylate could induce tinnitus through activation of TRPV1 in the rat auditory pathway. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.