Blockade of cochlear NMDA receptors prevents long-term tinnitus during a brief consolidation window after acoustic trauma

Neural Plast. 2007:2007:80904. doi: 10.1155/2007/80904.

Abstract

Tinnitus, the perception of sound in the absence of external acoustic stimulation, is a common and devastating pathology. It is often a consequence of acoustic trauma or drug toxicity. The neuronal mechanisms of tinnitus are neither yet fully understood nor are effective treatments available. Using a novel behavioral paradigm for measuring tinnitus in the rat based on tone-guided navigation, we show here that the development of long-term noise-induced tinnitus, the most prevalent and clinically important form of human tinnitus, can be abated by local administration of the NMDA antagonist "ifenprodil" into the cochlea in the first 4 days following the noise insult but not afterwards. This suggests that long-term tinnitus undergoes a consolidation-like process, resembling the ontogeny of items in long-term memory. Furthermore, this finding paves the way to potential therapeutic strategies for the prevention of chronic tinnitus once the noise insult had taken place.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Audiometry
  • Chronic Disease / prevention & control
  • Cochlea / drug effects*
  • Cochlea / physiopathology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / metabolism
  • Hearing / physiology
  • Male
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Time Factors
  • Tinnitus / drug therapy*
  • Tinnitus / physiopathology*
  • Treatment Outcome

Substances

  • Excitatory Amino Acid Antagonists
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • ifenprodil