GABAergic system participation in Spinacia oleracea induced antiseizure property against experimental epilepsy

Abstract

Pentylenetetrazole (PTZ) induced experimental epileptic model is widely studied for understanding the basic mechanism of human petit mal epilepsy. The proposed study has been undertaken to elucidate the effect of Spinacia oleracea (SO; common name: Spinach) leaves on PTZ induced epileptic convulsion as well as to assess the participation of GABAergic tone in the effect of SO. The anticonvulsant property of SO was depicted by seizure parameters, electrical activity of the brain (EEG analysis) and monoamine levels of serotonin (5-HT), dopamine (DA) & norepinephrine (NE) in different brain regions. The present experiment has been divided into two schedules. In first schedule thirty rats were grouped (5 groups) equally into Control (gr. 1), SO (gr. 2), PTZ (gr. 3), SO+PTZ (gr. 4) and Diazepam (DZ)+PTZ (gr. 5). In the second schedule in order to investigate the probable involvement of GABAergic system another twelve rats were equally divided into 2 groups such as PTX (Picrotoxin)+SO+PTZ (gr. A) and PTX+DZ+PTZ (gr. B). The results indicated that herbal pretreatment of aqueous SO extract prolonged the latency and reduced the duration of tonic-clonic seizures in PTZ induced animals and seizure score was also decreased. Thus SO can give protection against PTZ induced epileptic seizure. In the PTZ induced seizure model, the administration of PTX before SO, reversed the effect of SO in prolonging seizure latency and reducing the duration of tonic-clonic seizures. There was no significant difference between the latency and/or duration of seizure of rats of gr. A which received PTX+SO+PTZ and the group (gr. B) which received only SO+PTZ. This result indicated that SO may act by facilitating the inhibitory activity of the GABAergic system, probably through a competitive agonist action in the GABAA receptor site because PTX is a selective antagonist of GABAA receptor. EEG analysis of SO+PTZ group revealed significant abolition of - (1) high voltage spike discharges, (2) polyspikes, (3) bursts in SO pretreated PTZ induced rats compared to only PTZ induced rats. This indicates SO may lower the electrical excitability of neurons, thus decreased the high voltage spike discharges. Hence, protected the animals from the development of generalized tonic-clonic seizure. Following pretreatment with SO, 5-HT was increased and DA was in all brain regions of PTZ induced epileptic rats. The level of NE in SO+PTZ group showed no significant changes when compared with PTZ group. Present findings conclude that the oral administration of Spinacia oleracea leaves extract may suppress the PTZ induced epileptic seizures probably by increasing GABAergic tone either by acting on GABA receptor directly or by increasing serotonergic neurotransmitter which ultimately showed antiepileptic property through mediation of GABAergic tone. Further studies need to be done to clarify the mechanism of DA and NE.