PPARα antagonist could not significantly suppress the anticonvulsant effect of DHA in the amygdala kindling model of rat

Docosahexaenoic acid (DHA) is the most abundant and bioactive fatty acid in the brain. Recently, the application of DHA as supplementary has been considered for treatment and prevention of epilepsy. Peroxisome proliferator-activated receptors (PPARs) activation by DHA has been proposed as some therapeutic effect of DHA. We investigated the probable involvement of PPARα in the anticonvulsant effect of DHA in the amygdala kindling model of epilepsy. The study was performed in 2 groups of 8 kindled rats. Group1 received the most effective dose of DHA (1mM/10μl/rat) alone. Group2 pretreated by a sub-effective dose of PPARα antagonist, GW6471 (1μg/1μl/rat), then DHAadministered after 15min. Control groups received HPB10% and DMSO as the solvent of DHA and GW6471, respectively. All injections were performed intracerebroventricularly. The electrical stimulation was performed 15min, 1h, and 3h after DHA. Then, the incidence of generalized-clonic seizures (GS) was monitored. The percentage of full-kindled rats with no GS in group1 are 57, 28 and 42% in 15min, 1h and 3h, respectively. Protection was significant in 15min (p<0.05). In group2 were 37, 75 and 25% in 15min, 1h and 3h, respectively. Protection was significant in 1h (p<0.01). GW6471 couldn’t significantly suppress DHA anticonvulsant effect. Furthermore, along with GW6471, DHA anticonvulsant effect in 15min and 1h after injection insignificantly decreased and increased, respectively. Perhaps GW6471 has partial and transient inhibition on DHA effect. So, PPARα could be probably involved in DHA anticonvulsant effect against seizure induced by amygdala kindling.

کلیدواژه ها:

DHA ، PPARα ، GW6471 ، Seizure