m-Chlorophenylpiperazine exacerbates perception of salicylate-induced tinnitus in rats.
The serotonin receptor 5-HT2c agonist m-chlorophenylpiperazine (mCPP) has been widely used to induce anxiety-like states in animals and anxiety in humans. We here addressed the effect of an intraperitoneal injection of mCPP on the perception of tinnitus in a behavioural protocol based on an active avoidance paradigm. In control saline-treated animals, mCPP did not change compound action potential audiograms or measurable tinnitus. In contrast, mCPP to animals demonstrating salicylate-induced tinnitus exacerbated tinnitus perception by nearly twofold. We went on to test whether manipulation of the peripheral generator of tinnitus (i.e. the cochlea) could extinguish this exacerbated perception by applying the N-methyl-d-aspartate (NMDA) antagonist 7-chlorokynurenate (7-CK) into cochlear fluids using a 7-CK-soaked Gelfoam ball placed on the round window of each of the animals' two ears. In addition to blocking the tinnitus induced by salicylate alone, 50 microm of 7-CK clearly abolished tinnitus in animals receiving salicylate and an injection of mCPP. The demonstration that cochlear NMDA receptor blockade abolishes the exacerbated perception of tinnitus is highly relevant in terms of treatment. In addition to psychotherapeutic treatment that may help to attenuate an individual's perception of tinnitus, targeting cochlear NMDA receptors represents a promising therapeutic strategy, even in depressed or chronically anxious patients.
Guitton
Matthieu J
MJ
Inserm U 583/INM Hôpital St Eloi and Université Montpellier 1, Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, 80 rue A Fliche, BP 74103, 34091 Montpellier cedex 5, France.
Pujol
Rémy
R
Puel
Jean-Luc
JL
D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012459:Salicylates; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014012:Tinnitus / Q000139:chemically induced* / Q000523:psychology*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D012459:Salicylates; D017366:Serotonin Receptor Agonists; C015068:1-(3-chlorophenyl)piperazine