Effects of chronic salicylate on GABAergic activity in rat inferior colliculus

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.