Behavioral assessment and identification of a molecular marker in a salicylate-induced tinnitus in rats.

Abstract

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.

• Authors: K Kizawa, T Kitahara, A Horii, C Maekawa, T Kuramasu, T Kawashima, S Nishiike, K Doi, H Inohara
• Journal: Neuroscience (Neuroscience) Vol. 165 Issue 4 Pg. 1323-32 (Feb 17 2010) ISSN: 1873-7544 [Electronic] United States
• PMID: 19958810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Membrane Transport Modulators
• RNA, Messenger
• Salicylates
• TRPV Cation Channels
• Trpv1 protein, rat
• capsazepine
• Capsaicin

Topics

• Animals
• Auditory Pathways (drug effects, pathology, physiopathology)
• Behavior, Animal (physiology)
• Biomarkers (metabolism)
• Capsaicin (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Male
• Membrane Transport Modulators (pharmacology)
• Neuropsychological Tests
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Salicylates
• Spiral Ganglion (drug effects, pathology, physiopathology)
• TRPV Cation Channels (antagonists & inhibitors, metabolism)
• Time Factors
• Tinnitus (chemically induced, pathology, physiopathology)
• Up-Regulation (drug effects)