Department of Neuroscience, AstraZeneca R&D, SE-151 85 Södertälje, Sweden.
Brain Res. 2013 May 13;1510:48-62. doi: 10.1016/j.brainres.2013.03.013. Epub 2013 Mar 25.
Rats were trained in a two lever food reinforced operant procedure to discriminate a 8000 Hz pure tone stimulus from its absence. Responding on one lever was reinforced in the presence of the tone and responding on the other lever was reinforced when the tone was absent. Frequency generalization testing yielded an inverted U-shaped function, whereas sound pressure level generalization testing yielded a continuous decrease in responding on the tone associated lever with decreasing sound pressure levels. The administration of sodium salicylic acid (150-450 mg/kg) generated responding on the tone associated lever suggesting that salicylic acid induced an experience that had commonalities with the percept of the training tone stimulus. After exposure to intense sound, responding consistent with the presence of tinnitus was achieved and Lidocaine failed to reduce tinnitus behavior. The use of a two choice design helped avoid confounding factors induced by drug induced side effects. Further, since no auditory cues were employed in the test situation the model achieves resistance to potential bias due to hearing impairment and hyperacusis. We propose that this model may be useful in detecting tinnitus.
大鼠在双杠食物强化操作性条件反射程序中接受训练,以区分 8000 Hz 纯音刺激与其不存在。在有音调时,对一个杠杆的反应被强化,而在音调不存在时,对另一个杠杆的反应被强化。频率泛化测试产生了一个倒 U 形的函数,而声压级泛化测试则导致与音调相关的杠杆上的反应随着声压级的降低而连续下降。水杨酸钠(150-450mg/kg)的给药导致与音调相关的杠杆上的反应,表明水杨酸钠引起的体验与训练音调刺激的感知有共同之处。暴露于强烈的声音后,出现了与耳鸣一致的反应,而利多卡因未能减少耳鸣行为。使用二选一设计有助于避免由药物引起的副作用引起的混杂因素。此外,由于在测试情况下没有使用听觉提示,该模型对由于听力损伤和听觉过敏引起的潜在偏差具有抵抗力。我们提出,该模型可能有助于检测耳鸣。