Possible Interaction of Oxidative Stress, Inflammatory, and Nitric Oxide Pathways in the Anticonvulsant Effect of Vortioxetine on Pentylenetetrazole-Induced Seizures in Rats

Antidepressants are known to demonstrate various effects on the nervous system. As a new antidepressant, vortioxetine is used for major depression in adult patients, with no clear indication of epileptic seizures and underlying mechanisms. The aim here was to examine the impact and possible mechanisms of vortioxetine on pentylenetetrazole-induced epileptic seizures in rats. The rats were randomly divided into 5 groups, each with 6 rats. Group 1 was control, Group 2 was administered saline (1 mL/kg/day serum physiologic), Group 3 was given (1 mg/kg/day diazepam), and Groups 4 and 5 were administered vortioxetine (2.5 and 5 mg/kg/day). The experimental groups (Groups 2-5) were given the drugs for a total of 7 days. Pentylenetetrazole (45 mg/kg) was administered on day 7 to all but the control group. Behavioural testing was performed using passive avoidance and open-field tasks. Total antioxidant status (TAS), total oxidant status (TOS), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP) caspase-3, and caspase-9 levels were measured using a commercial kit. The groups receiving vortioxetine (2.5 and 5 mg/kg) were found to have delayed epileptic seizure onset times and reduced seizure stages with improved memory impairment after seizures. These groups also had increased TAS levels and decreased TOS levels in the cortex and hippocampus. Additionally, TNF-alpha, IL-1 beta, nNOS, sGC, cGMP, caspase-3, and caspase-9 levels in the cortex and hippocampus were statistically significantly lower for these groups. Vortioxetine pretreatment was determined to have protective effects on pentylenetetrazole-induced seizures in rats, with alleviated seizures and improved memory impairment, oxidative stress, inflammation, and apoptosis. The mechanisms of vortioxetine may involve the inhibition of oxidative stress, inflammation, and the nNOS/sGC/cGMP signalling pathway.