Blockade of cochlear NMDA receptors prevents long-term tinnitus during a brief consolidation window after acoustic trauma.
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.
Guitton
Matthieu J
MJ
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Dudai
Yadin
Y
D000161:Acoustic Stimulation; D000818:Animals; D001299:Audiometry; D002908:Chronic Disease / Q000517:prevention & control; D003051:Cochlea / Q000187:drug effects* / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism; D006309:Hearing / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014012:Tinnitus / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C010739:ifenprodil