Lobarinas Edward, Sun Wei, Cushing Ross, Salvi Richard
Center for Hearing and Deafness, Hearing Research Lab, University of Buffalo, 215 Parker Hall, Buffalo, NY 14214, USA.
Hear Res. 2004 Apr;190(1-2):109-14. doi: 10.1016/S0378-5955(04)00019-X.
A behavioral technique was developed that allowed the onset and recovery of tinnitus to be measured in individual rats treated with different doses of salicylate. Food-restricted rats were self-trained to lick for water during the time between scheduled delivery of food pellets, i.e., schedule-induced polydipsia (SIP). SIP-induced licking was placed under stimulus control by administering foot shock if licks occurred when sound (one of six stimuli, 40 dB SPL) was present; rats were allowed to lick during quiet. After the number of licks-in-quiet (correct response) exceeded 90% of total licks, rats were treated with saline and four different doses of salicylate (50, 100, 150 and 350 mg/kg, intraperitoneally (i.p.); 2 days). Performance was assessed before, during and after treatment. Licks-in-sound remained extremely low with saline and all four salicylate doses indicating that the sounds were audible under all treatment conditions. Licks-in-quiet remained high during the saline control and 50 mg/kg dose of salicylate, behavior consistent with the absence of tinnitus. However, licks-in-quiet showed a statistically significant decline with the 150 and 350 mg/kg dose, behavior consistent with the presence of tinnitus. Licks-in-quiet gradually recovered to baseline level 2-3 days following high-dose salicylate treatments, behavior consistent with the gradual disappearance of tinnitus. The salicylate dose needed to induce tinnitus and the length of recovery are consistent with previous reports, providing support for the method. The ability to obtain sequential estimates of tinnitus-like behavior in an animal after administering a tinnitus-inducing agent could aid in understanding the underlying neural mechanisms and assessing potential treatments.
开发了一种行为技术,可用于测量用不同剂量水杨酸盐治疗的个体大鼠耳鸣的发作和恢复情况。对食物受限的大鼠进行自我训练,使其在预定投喂食物颗粒的时间段内舔水,即定时诱导多饮(SIP)。如果在声音(六种刺激之一,40 dB声压级)出现时发生舔舐行为,则通过施加足部电击将SIP诱导的舔舐行为置于刺激控制之下;大鼠在安静时可以舔舐。在安静时的舔舐次数(正确反应)超过总舔舐次数的90%后,给大鼠注射生理盐水和四种不同剂量的水杨酸盐(50、100、150和350 mg/kg,腹腔注射(i.p.);持续2天)。在治疗前、治疗期间和治疗后评估大鼠的行为表现。使用生理盐水和所有四种水杨酸盐剂量时,有声音时的舔舐次数都极低,这表明在所有治疗条件下声音都是可听见的。在生理盐水对照和50 mg/kg剂量的水杨酸盐治疗期间,安静时的舔舐次数仍然很高,这一行为与无耳鸣一致。然而,在150和350 mg/kg剂量时,安静时的舔舐次数出现了统计学上的显著下降,这一行为与耳鸣的存在一致。在高剂量水杨酸盐治疗后2 - 3天,安静时的舔舐次数逐渐恢复到基线水平,这一行为与耳鸣的逐渐消失一致。诱导耳鸣所需的水杨酸盐剂量和恢复时间与先前的报道一致,为该方法提供了支持。在给动物施用耳鸣诱导剂后,能够对类似耳鸣的行为进行连续评估,这有助于理解潜在的神经机制并评估潜在的治疗方法。