title: Evidence that Memantine Reduces Chronic Tinnitus Caused by Acoustic Trauma in Rats.
abstract: Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Increasing evidence suggests that tinnitus is caused by neuronal hyperactivity in auditory brain regions, either due to a decrease in synaptic inhibition or an increase in synaptic excitation. One drug investigated for the treatment of tinnitus has been the uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, memantine, although the evidence relating to it has been unconvincing to date. We re-investigated the effects of memantine on the behavioral manifestations of tinnitus induced by acoustic trauma (a 16-kHz, 110-dB pure tone presented unilaterally for 1 h) in rats. We used a conditioned lick suppression model in which lick suppression was associated with the perception of high frequency sound resembling tinnitus and a suppression ratio (SR) was calculated by comparing the number of licks in the 15-s period preceding the stimulus presentation (A) and the 15-s period during the stimulus presentation (B), i.e., SR = B/(A + B). Acoustic trauma resulted in a significant increase in the auditory brainstem-evoked response (ABR) threshold in the affected ear (P ≤ 0.0001) and a decrease in the SR compared to sham controls in response to 32 kHz tones in five out of eight acoustic trauma-exposed animals. A 5-mg/kg dose of memantine significantly reduced the proportion of these animals which exhibited tinnitus-like behavior (2/5 compared to 5/5; P ≤ 0.006), suggesting that the drug reduced tinnitus. These results suggest that memantine may reduce tinnitus caused by acoustic trauma.
authors.affiliation: Department of Pharmacology and Toxicology, Brain Health Research Centre, School of Medical Sciences, University of Otago Dunedin, New Zealand.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zheng
authors.forename: Emily
authors.initials: E
authors.lastname: McNamara
authors.forename: Lucy
authors.initials: L
authors.lastname: Stiles
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Darlington
authors.forename: Paul F
authors.initials: PF
authors.lastname: Smith