title: The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats.
abstract: Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The present study confirms the role of cochlear NMDA receptors in the induction of salicylate-induced tinnitus.
authors.affiliation: Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: M
authors.initials: M
authors.lastname: Ralli
authors.affiliation: Institute of Physiology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: D
authors.initials: D
authors.lastname: Troiani
authors.affiliation: Institute of Physiology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: M V
authors.initials: MV
authors.lastname: Podda
authors.affiliation: Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: F
authors.initials: F
authors.lastname: Paciello
authors.affiliation: Institute of Physiology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: S L M
authors.initials: SL
authors.lastname: Eramo
authors.affiliation: Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: E
authors.initials: E
authors.lastname: de Corso
authors.affiliation: Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, University at Buffalo, NY.
authors.forename: R
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: G
authors.initials: G
authors.lastname: Paludetti
authors.affiliation: Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Roma, Italy;
authors.forename: A R
authors.initials: AR
authors.lastname: Fetoni
mesh_terms: D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates; D014012:Tinnitus / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D012459:Salicylates; D016202:N-Methylaspartate; D008559:Memantine
keywords: Memantine; NDMA receptors; Rats; Salicylate; Startle reflex; Tinnitus