Auditory Neural Plasticity in Tinnitus Mechanisms and Management

Figure 1

Possible therapeutic mechanism of TCAs on tinnitus. TCAs block the 5-HT_2A receptor, thus preventing 5-HT from binding to the 5-HT_2A receptor and activating the PLC-IP₃/DAG-PKC pathway and thus impairing downstream microtubule-dependent glycine receptor transport. This in turn acts as a barrier to glycine receptor binding on the surface of the cell membrane followed by a reduction of chloride influx and thus leading to a decrease in tonic current and an increase in intracellular potential and excitability. TCAs: tricyclic antidepressants; 5-HT_2AR:5-hydroxytryptamine receptor _2A receptor; PIP₂: phosphatidylinositol 4,5-bisphosphate; PLC: phospholipase C; DAG: diacylglycerol; PKC: protein kinase C; IP₃: inositol 1,4,5-trisphosphate.