Behavioral assessment and identification of a molecular marker in a salicylate-induced tinnitus in rats.
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.
Kizawa
K
K
Department of Otolaryngology-Head and Neck Surgery, Osaka University, School of Medicine, Suita-City, Osaka, Japan.
Kitahara
T
T
Horii
A
A
Maekawa
C
C
Kuramasu
T
T
Kawashima
T
T
Nishiike
S
S
Doi
K
K
Inohara
H
H
D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009483:Neuropsychological Tests; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D014012:Tinnitus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects
D015415:Biomarkers; D049990:Membrane Transport Modulators; D012333:RNA, Messenger; D012459:Salicylates; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C071423:capsazepine; D002211:Capsaicin