Effects of chronic salicylate on GABAergic activity in rat inferior colliculus

• Published in: Hearing research Vol. 147; no. 1; pp. 175 - 182
• Main Authors: Bauer, C.A, Brozoski, T.J, Holder, T.M, Caspary, D.M
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2000; Elsevier
• Subjects: Animals; Auditory plasticity; Biological and medical sciences; Drug toxicity and drugs side effects treatment; GABA; GAD; gamma-Aminobutyric Acid - metabolism; Glutamate Decarboxylase - metabolism; Humans; Inferior Colliculi - drug effects; Inferior Colliculi - metabolism; Inferior colliculus; Kinetics; Male; Medical sciences; Muscimol - metabolism; Neuronal Plasticity; Pharmacology. Drug treatments; Rat; Rats; Receptors, GABA-A - metabolism; Salicylate; Salicylic Acid - toxicity; Tinnitus; Tinnitus - chemically induced; Toxicity: respiratory system, ent, stomatology; Salicylate; Auditory plasticity; Rat; Inferior colliculus; GABA; GAD; Tinnitus; Salicylic acid; Enzyme; Toxicity; Rodentia; Central nervous system; Auditory disorder; Lyases; Glutamate decarboxylase; Carbon-carbon lyases; Vertebrata; Mammalia; Colliculus inferior; Carboxy-lyases; Animal; Plasticity; Neurotransmitter; ENT disease; Auditory pathway; Gabaergic receptor A; Brain (vertebrata); Ototoxicity
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(00)00130-1

It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA A receptor in auditory brainstem structures of Long–Evans rats chronically 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 behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [ 3H]muscimol saturation analysis data revealed a significant ( P<0.05) reduction in K d 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 structures. This suggests that GAD expression and GABA A receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.