Abscisic acid attenuates pentylenetetrazole-induced seizures and oxidative stress in adult male rats: evidence for GABAergic involvement

Abstract

Epilepsy is a common neurological disorder, and many patients remain resistant to available antiepileptic drugs. This study investigated the effects of intracerebroventricular (ICV) administration of abscisic acid (ABA), a plant-derived compound with antioxidant and anti-inflammatory properties, in a pentylenetetrazole (PTZ)-induced seizure model. Fifty-six adult male rats were divided into eight groups: Control, Sham+PTZ, PTZ, diazepam+PTZ, three ABA-treated groups (2.5, 5, and 10 µg/rat for five days), and a bicuculline+ABA+PTZ group to assess GABAergic involvement. Seizure severity was assessed using Racine’s scale, anxiety-like behavior by the elevated plus maze (EPM) and open field tests (OFT), and hippocampal oxidative stress markers, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), using ELISA. PTZ induced severe seizures, increased anxiety-like behaviors, elevated MDA levels, and reduced SOD activity (all p<0.001). ABA, particularly at 10 μg/rat, attenuated seizure severity, prolonged seizure latency, improved anxiety-like behaviors, decreased MDA levels, and restored SOD and CAT activities, with the greatest effects observed at 10 µg/rat. Bicuculline partially attenuated the anticonvulsant and antioxidant effects of ABA, indicating the involvement of GABAergic signaling. ABA exerts anticonvulsant, anxiolytic, and antioxidant effects in PTZ-induced seizure, at least partly through modulation of the GABAergic system, suggesting its potential as a therapeutic candidate for epilepsy.