Vortioxetine Increases Absence-Like Seizures in WAG/Rij Rats but Decreases Penicillin- and Pentylenetetrazole-Induced Seizures in Wistar Rats

Abstract

Aim: Depression is the major psychiatric disorder in patients with epilepsy. Vortioxetine is a novel antidepressant drug for the treatment of major depressive disorders. In the present study, effects of vortioxetine were evaluated in different experimental epilepsy models of rats. Materials and methods: Fifty-six adult male Wistar rats and 28 WAG/Rij rats were divided into 12 groups of 7 rats each. Experiments were conducted with penicillin (500 IU, i.c.) and pentylenetetrazole models (50 mg/kg, intraperitoneally (i.p.)) in Wistar rats and genetic absence epileptic WAG/Rij rats. The vortioxetine (1, 5, or 10 mg/kg, i.p.) was evaluated in these three models. All groups were compared with their control groups. Results: In the penicillin-induced seizure model, 1, 5, or 10 mg/kg vortioxetine administration significantly decreased mean spike frequency. In the pentylenetetrazole-induced seizure model, 1, 5, or 10 mg/kg vortioxetine demonstrated a significant dose-dependent decrease in mean spike frequency, an increase in the latency to minor and major seizures, and a decrease in total duration of major seizure and convulsion stage. In genetic absence epileptic WAG/Rij rats, 1 mg/kg vortioxetine caused no significant alteration in the number and duration of SWDs compared to the controls, while 5 and 10 mg/kg doses of vortioxetine increased the number and duration of SWDs. Amplitude of the epileptiform activity did not change in any of the experimental epilepsy models. Conclusion: The results of this study suggested that vortioxetine has anticonvulsant activity in penicillin- and pentylenetetrazole-induced seizure models. However, it exhibited proconvulsant activity in the absence epileptic WAG/Rij rats. © 2021 Elsevier Inc.