It is well accepted that salicylate ototoxicity results in reversible tinni
tus in humans. Salicylate-induced tinnitus may be an example of plasticity
of the central auditory system and could potentially serve as a model to fu
rther understand mechanisms of tinnitus generation. This study examined lev
els of glutamic acid decarboxylase (GAD) and the binding characteristics of
the GABA(A) receptor in auditory brainstem structures of Long-Evans rats c
hronically treated with salicylate. Western blotting revealed a significant
63% (P < 0.008) elevation of GAD levels in the inferior colliculus (IC) of
salicylate-treated subjects. This occurred in subjects demonstrating behav
ioral evidence of tinnitus. Muscimol saturation analysis was indicative of
a salicylate-related increase in receptor affinity. Linear regression of [H
-3]muscimol saturation analysis data revealed a significant (P < 0.05) redu
ction in Kd values in whole IC (-48%), as well as in the central nucleus of
IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%
). The number of GABA(A) binding sites (B-max) were also significantly (P <
0.05) decreased. These changes were observed only in central auditory stru
ctures. This suggests that GAD expression and GABA(A) receptor binding char
acteristics may be altered with chronic exposure to sodium salicylate and t
hese changes may represent aberrant plasticity clinically experienced as ti
nnitus. (C) 2000 Elsevier Science B.V. All rights reserved.