Increased metabolic activity and hysteretic enhanced GABA(A) receptor binding in a rat model of salicylate-induced tinnitus.

Tinnitus is relevant to neural hyperactivity in the central nervous system (CNS). Normal quantity and functioning of the γ-aminobutyric acid (GABA) receptor are crucial for maintaining the balance between excitation and inhibition in the brain. In this study, we applied a rat model of tinnitus via long-term salicylate administration. The combination of the gap pre-pulse inhibition of acoustic startle (GPIAS) and pre-pulse inhibition (PPI) tests were used to detect tinnitus-like behavior, and rats receiving 7 or 14 consecutive days of salicylate administration showed evidence of tinnitus. After positron emission tomography (PET) scan, we found that the metabolic activity was increased after salicylate treatment followed by enhanced GABAA receptor binding with cessation of salicylate administration in the auditory cortex (AC), medial prefrontal cortex (mPFC), hippocampus (HP), cingulate cortex (CiC) and insular (InC). The inferior colliculus (IC) showed an elevated metabolic activity with no change in the GABAA receptor binding. All the alterations returned to baseline several days after cessation of salicylate treatment despite a mismatch between the time-course of them. By contrast, we found alterations in neither the metabolic activity nor the GABAA receptor binding in the amygdala (AMY) and cerebellum (CRB). These findings indicate that enhanced neural activity in the auditory and limbic system may contribute to the development of tinnitus, while the hysteretic increase of GABAA receptor binding in specific areas of the CNS may be a compensation for hyperactivity, which may be involved in tinnitus relieving.

Wu C ，Bao W ，Yi B ，Wang Q ，Wu X ，Qian M ，Zuo C ，Huang Z ... -  《-》

Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS.

Yi B ，Hu S ，Zuo C ，Jiao F ，Lv J ，Chen D ，Ma Y ，Chen J ，Mei L ，Wang X ，Huang Z ，Wu H ... -  《Scientific Reports》

Changes in GABA and glutamate receptors on auditory cortical excitatory neurons in a rat model of salicylate-induced tinnitus.

Wu C ，Wu X ，Yi B ，Cui M ，Wang X ，Wang Q ，Wu H ，Huang Z ... -  《American Journal of Translational Research》

Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat.

Hu SS ，Mei L ，Chen JY ，Huang ZW ，Wu H ... -  《-》

Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats.

Yi B ，Wu C ，Shi R ，Han K ，Sheng H ，Li B ，Mei L ，Wang X ，Huang Z ，Wu H ... -  《-》