Hamid Reza Sadeghnia - Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Ali Reza Taji - Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
Fatemeh Forouzanfar - Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Hossein Hosseinzadeh - Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): K+ channel blocker ۴-aminopyridine (۴-AP) stimulates the release of glutamate from nerve terminals and induces seizures. Berberine as a potential herbal drug exerts several pharmacological actions on the central nervous system including anxiolytic, anticonvulsant, and neuroprotective properties. The present study aimed to investigate the effect of berberine on seizure onset and time course of the extracellular levels of excitatory amino acids (EAA), glutamate and aspartate, changes produced by ۴-AP in rat hippocampus. Materials and Methods: The rats were given either saline or berberine (۵۰, ۱۰۰ and ۲۰۰ mg/kg, IP) ۴۰ min before administration of ۴-AP (۱۵ mg/kg, IP) and the onset of seizure was recorded. A group of rats also received diazepam (DZP, ۱۵ mg/kg, IP) ۲۰ min prior to ۴-AP administration. Hippocampal extracellular levels of EAA were also measured using microdialysis assay. Analysis of the dialysate samples was performed by reversed-phase high performance liquid chromatography (HPLC) with precolumn derivatization with o-phthaldialdehyde and fluorescence detection. Results: Our findings suggest that berberine significantly delayed the seizure onset following ۴-AP injection. There was a considerable increase in the extracellular glutamate and aspartate levels in ۴-AP treated rats and ۴-AP-evoked release of EAA was sharply reduced (about ۴-۵ fold especially at ۲۰ min after ۴-AP administration) in berberine treatment groups. Conclusion: The results of present study show that berberine attenuates ۴-AP induced seizures by decreasing hippocampal aspartate and glutamate release in rats.

Barberry, Berberis vulgaris, Berberine, Excitatory amino acids, ۴-Aminopyridine (۴-AP), Seizure