[Evaluating effects of some medicine on tinnitus with animal behavioral model in rats].
OBJECTIVE
To develop a valid behavioral animal model of tinnitus and to determine the animals whether have the perception of tinnitus and to evaluate effects of nimodipine and Chinese herbs on tinnitus using the behavioral model.


METHODS
Adult male albino rats (n = 60) were fell evenly and randomly into ten groups. Animals in Group I and II were administrated sodium salicylate 350 mg/kg/d (i.p.). Instead, animals in control groups (Group III and IV) were saline injected. Pure tone (8 kHz, 65 dBSPL) was given to rats in Group V and VI instead of sodium salicylate. Nimodipine (1 mg/kg) were administrated to animals in Group VII and VIII. Gushenshuerfang, one kind of Chinese herbs were administrated to animals in Group IX and X. Medicine or pure tone were being given to all animals in Group I, III, V, VII, IX before conditioned reflex. Animals in Group II, IV, VI, VIII, X began to have medicine or pure tone after conditioned reflex. Thirsty animals (deprived of water for several days) were breeded in sound-proofed room and listened a persistent white noise (55 dB SPL) and trained daily with our instrument system, according to the procedure based on Pavlovian conditioned suppression paradigm. Subjects were permitted to lick water at an automatic dispenser during daily training sessions and the number of licks was recorded automatically. Noise offset (silence) was the conditioned stimulus and the electrical shock was the unconditioned stimulus. After two or three days training, subjects learnt rapidly to associate noise offset with shock and then established a behavioral conditioned reflex. Because of shock fear they decrease or even stop licking with the presentations of conditioned stimulus. However, subjects gradually forgot or ignored the fear without any shock present in extinction test sessions.


RESULTS
Animals' licking recovered to their pre-training levels respectively at the following days: Group I--5 days, Group II--2 days, both Group III and IV--4 days, Group V--5 days, Group VI--2 days, Group VII--5 days, Group VIII--4 days, Group IX--5 days, Group X--4 days. There were much significant differences among all groups and all training days (F test, P < 0.001). Above results provided sufficient evidence for that tinnitus was induced by salicylate and tinnitus presented with noise offset. In group I, tinnitus became additional conditioned stimulus. Therefore, the fear of animals was much severe and the numbers of licking were much fewer. Extinction lasted longer. In group II, animals ignored the noise offset much easily and the extinction lasted much shorter. Moreover, results from group V and VI, pure tone instead of salicylate, indicated that sensation (tinnitus) sounded like pure tone. The groups VII, VIII, IX, X demonstrated that nimodipine and Gushenshuerfang, one kind of Chinese herbs can cure the tinnitus induced by salicylate.


CONCLUSIONS
All behavioral evidence indicated that animals perceived tinnitus induced by salicylate and this animal model could be used in evaluating curative effects of some medicine on tinnitus.
Wang
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H
Institute of Otorhinolaryngology, Chinese PLA General Hospital, Beijing 100853, China. wht301@263.net
Jiang
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S
Yang
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W
Han
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D000818:Animals; D001307:Auditory Perception / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D008517:Phytotherapy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate; D014012:Tinnitus / Q000139:chemically induced / Q000188:drug therapy*
D004365:Drugs, Chinese Herbal; D009553:Nimodipine; D012980:Sodium Salicylate