Effects of chronic salicylate on GABAergic activity in rat inferior colliculus.
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 [(3)H]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.
Bauer
C A
CA
Southern Illinois University School of Medicine, Springfield, IL 62794-9662, USA. cbauer@siumed.edu
Brozoski
T J
TJ
Holder
T M
TM
Caspary
D M
DM
D000818:Animals; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007245:Inferior Colliculi / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009473:Neuronal Plasticity; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D020156:Salicylic Acid / Q000633:toxicity*; D014012:Tinnitus / Q000139:chemically induced; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D020156:Salicylic Acid