© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Alpha2-adrenoreceptor (α2-AR) is a noradrenergic receptor that is frequently studied for modulation of seizure activity. However, the precise role of this receptor agonists in regulating seizure activity is still unclear. Our aim in this study was to investigate the effects of α2-AR agonist dexmedetomidine (DEX) and atipamezole (α2-AR antagonist, ATI) on seziures in rats. In the study, 32 adult male Wistar Albino rats (weighing 220–260 g) were used. To induce seizures in rats, pentylenetetrazole (PTZ, 35 mg/kg) was injected intraperitoneally (i.p.) and seizure stages were determined according to the Racine scale. After induction of seizures, DEX (0.1 mg/kg, i.p.) and ATI (1 mg/kg, i.p.) were administered to rats and their effects determined on seizures. GABA levels of the brain hippocampal tissue sample were measured using an ELISA kit and c-Fos positive cells of the dentate gyrus and hippocampal regions were quantitatively analyzed with Image J software. The results showed that DEX decreased the seizure stages according to the Racine scale, significantly prolonged the onset time of first myoclonic jerk (FMJ) and reduced the number of spikes and percentage seizure duration (p < 0.05). In contrast, ATI increased the seizure stage, the number of spikes and percentage seizure duration. The hippocampal GABA level was significantly decreased in rats with only PTZ injection (p < 0.05). In addition, DEX reduced the number of c-Fos positive cells in dentate gyrus and the hippocampal CA1 and CA3 regions. In conclusion, our findings showed that α2-AR agonist DEX had a reducing activity on PTZ-induced seizure, while α2-AR antagonist ATI facilitated seizure formation.