Abscisic Acid Attenuates Pentylenetetrazole-Induced Seizures and Oxidative Stress in Adult Male Rats: Evidence for GABAergic Involvement

Abstract

Background: 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.

Method: 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.

Results: 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.

Conclusions: 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.