Agomelatine attenuates calcium signaling and apoptosis via the inhibition of TRPV1 channel in the hippocampal neurons of rats with chronic mild stress depression model.

Chronic stress plays a key role in inducing various clinical disorders through mechanistic pathways, including oxidative stress and apoptosis. Transient receptor potential vanilloid 1 (TRPV1) channels, which are permeable to cations, mainly Ca2+, are susceptible to oxidative stress. Agomelatine (AGOM) is an antidepressant drug analogous to the antioxidant melatonin hormone, although its action has not been fully clarified yet. We aimed to investigate the protective role of AGOM on TRPV1-induced Ca2+ signaling and apoptosis in rats with chronic mild stress (CMS). The rats were divided into six main groups: control, dimethyl sulfoxide (DMSO), AGOM, CMS, CMS+DMSO, and CMS+AGOM. Five weeks of CMS were applied to rats in the CMS groups. The induction of CMS was confirmed with the sucrose preference test. The AGOM treatments were administered in the last three weeks of the experiment. The depression-like behavior, TRPV1-mediated cytosolic Ca2+ influx, lipid peroxidation, apoptosis, caspase - 3, and - 9 levels increased in the hippocampal neurons of CMS groups, although cell viability level was diminished by the CMS exposure. However, AGOM treatment downregulated stress-related behaviors, hippocampal oxidant and apoptotic markers by modulating the TRPV1 activity. In conclusion, TRPV1-mediated Ca2+ signaling and apoptosis may play a role in the etiopathogenesis of experimental depression. By regulating these changes with AGOM treatment, a positive contribution may be made to depression treatment.