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

Neuroscience. 2010 Feb 17;165(4):1323-32. doi: 10.1016/j.neuroscience.2009.11.048. Epub 2009 Dec 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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