Zheng Yiwen, McNamara Emily, Stiles Lucy, Darlington Cynthia L, Smith Paul F
Department of Pharmacology and Toxicology, Brain Health Research Centre, School of Medical Sciences, University of Otago Dunedin, New Zealand.
Front Neurol. 2012 Aug 15;3:127. doi: 10.3389/fneur.2012.00127. eCollection 2012.
Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Increasing evidence suggests that tinnitus is caused by neuronal hyperactivity in auditory brain regions, either due to a decrease in synaptic inhibition or an increase in synaptic excitation. One drug investigated for the treatment of tinnitus has been the uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, memantine, although the evidence relating to it has been unconvincing to date. We re-investigated the effects of memantine on the behavioral manifestations of tinnitus induced by acoustic trauma (a 16-kHz, 110-dB pure tone presented unilaterally for 1 h) in rats. We used a conditioned lick suppression model in which lick suppression was associated with the perception of high frequency sound resembling tinnitus and a suppression ratio (SR) was calculated by comparing the number of licks in the 15-s period preceding the stimulus presentation (A) and the 15-s period during the stimulus presentation (B), i.e., SR = B/(A + B). Acoustic trauma resulted in a significant increase in the auditory brainstem-evoked response (ABR) threshold in the affected ear (P ≤ 0.0001) and a decrease in the SR compared to sham controls in response to 32 kHz tones in five out of eight acoustic trauma-exposed animals. A 5-mg/kg dose of memantine significantly reduced the proportion of these animals which exhibited tinnitus-like behavior (2/5 compared to 5/5; P ≤ 0.006), suggesting that the drug reduced tinnitus. These results suggest that memantine may reduce tinnitus caused by acoustic trauma.
主观性耳鸣是一种会感知到幻听的慢性神经障碍。越来越多的证据表明，耳鸣是由听觉脑区的神经元活动亢进引起的，这要么是由于突触抑制减少，要么是由于突触兴奋增加。一种被研究用于治疗耳鸣的药物是非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂美金刚，尽管迄今为止与之相关的证据并不令人信服。我们重新研究了美金刚对大鼠声创伤（单侧呈现16kHz、110dB纯音1小时）诱发耳鸣行为表现的影响。我们使用了一种条件性舔舐抑制模型，其中舔舐抑制与类似于耳鸣的高频声音感知相关，并通过比较刺激呈现前15秒内的舔舐次数（A）和刺激呈现期间15秒内的舔舐次数（B）来计算抑制率（SR），即SR = B /（A + B）。与假手术对照组相比，声创伤导致受影响耳朵的听觉脑干诱发电位（ABR）阈值显著升高（P≤0.0001），并且在八只接受声创伤的动物中有五只对32kHz音调做出反应时，SR降低。5mg/kg剂量的美金刚显著降低了表现出耳鸣样行为的动物比例（2/5，而之前为5/5；P≤0.006），表明该药物减轻了耳鸣。这些结果表明美金刚可能减轻由声创伤引起的耳鸣。
