This study aimed to examine the effects of vortioxetine, a novel antidepressant, on epileptiform activity in pentylenetetrazole (PTZ)-induced kindling model in rats. For this purpose, 20 male Wistar Albino rats were used, and epileptiform activity was induced by injection of PTZ (35mg/kg, i.p., three times a week). In the vortioxetine groups, vortioxetine (5mg/kg and 10mg/kg) was administered before the kindling process. During the kindling process, the Fisher and Kittner seizure scales were used to score seizure severity. After kindling, novel object recognition (NOR) tests were performed to evaluate the cognitive performance of rats. Electrodes were implanted into the fully kindled animals for ECoG recordings. In the PTZ group, the number of total spikes was 1367±136 spikes/20minutes. First myoclonic jerks decreased while seizure severity and total spike count increased in the PTZ group. On the other hand, the total spike number and seizure severity significantly decreased and first myoclonic jerks increased in the vortioxetine groups compared to the PTZ group. Based on the NOR test, vortioxetine administration markedly raised the discrimination index compared to the PTZ group. Electrophysiological and behavioural data from the present study suggest that vortioxetine, a novel drug, plays a critical role in controlling PTZ-induced epileptiform activity in rats. Vortioxetine may therefore be a valuable candidate to prevent seizure activity and treat cognitive deficits associated with epilepsy.