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 per-ceived. 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 com-paring 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 signicant increase in the auditory brainstem-evoked response (ABR) thresh-old in the affected ear (P ≤0.0001) and a decrease in the SR compared to sham controls in response to 32 kHz tones in ve out of eight acoustic trauma-exposed animals. A 5-mg/kg dose of memantine signicantly 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. © 2012 Zheng, McNamara, Stiles, Darlington and Smith.