Salicylate- and quinine-induced tinnitus and effects of memantine.
CONCLUSIONS
Memantine, an antiglutamatergic drug, has been proposed as a treatment for tinnitus.


OBJECTIVE
The purpose of this study was to determine if memantine would prevent salicylate-induced tinnitus. Local field potentials were also recorded from auditory cortex to determine what effect salicylate, memantine, and the combination of both drugs would have on evoked potential amplitudes.


METHODS
Schedule induced polydipsia-avoidance conditioning was used to identify the doses of salicylate or quinine that reliably induced tinnitus in rats. Rats were trained to lick for water during quiet intervals and avoid licking during sound intervals.


RESULTS
Rats injected with saline or a low dose of sodium salicylate or quinine failed to develop tinnitus-like behaviors. However, high doses of salicylate (150-300 mg/kg/day) or quinine (100-150 mg/kg/day) greatly reduced licks-in-quiet, behavior consistent with the presence of tinnitus. Licks-in-quiet increased slightly when memantine (1.5 or 3 mg/kg/day) was co-administered with salicylate; however, the effect was not statistically significant or dose-dependent. These results indicate that memantine does not completely suppress salicylate-induced tinnitus. Cortical auditory evoked potential amplitude increased after salicylate treatment; co-administration of memantine failed to block this salicylate-induced increase.
Lobarinas
E
E
University at Buffalo, Buffalo, NY 14214, USA.
Yang
G
G
Sun
W
W
Ding
D
D
Mirza
N
N
Dalby-Brown
W
W
Hilczmayer
E
E
Fitzgerald
S
S
Zhang
Liyan
L
Salvi
R
R
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001303:Auditory Cortex / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use*; D016202:N-Methylaspartate / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology / Q000627:therapeutic use*; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D014012:Tinnitus / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010276:Parasympatholytics; D016202:N-Methylaspartate; D011803:Quinine; D020156:Salicylic Acid; D008559:Memantine