Investigating the Synergistic Effect of Palmitoylethanolamide and Ganaxolone in PTZ-induced Tonic-clonic Seizures

Abstract

Background and Aim: Anticonvulsive effects of neurosteroids were shown in animal models. Endocannabinoids modulate neuronal excitability. In this study, we investigated the synergism of the simultaneous application of Palmitoylethanolamide (PEA) as an endocannabinoid and Ganaxolone as a neurosteroid, on tonic-clonic seizures induced by PTZ. Materials and Methods: Adult male Wistar rats were used. The tonic-colonic seizure was induced through a single injection of PTZ (80 mg/kg) and seizure stages were monitored for 30 minutes. Ganaxolone (10 mg/kg) and PEA (40 mg/kg) dissolved in DMSO were injected alone and simultaneously intra-peritoneal 15 minutes before the PTZ injection. Delay to the seizure stages, duration of the stages, and mortality due to seizures were measured. Results: PEA had no significant effect on seizure indices. Ganaxolone significantly increased delay to seizure stages 1-4 and reduced the duration of stage 5, also mortality of seizures was reduced in comparison with PTZ group from 50% to 16%. Simultaneous injection of PEA and Ganaxolone significantly delayed seizure stages 1-5 in comparison with both PTZ and Ganaxolone groups and reduced the duration of stage 5. Also, mortality due to seizures was reduced in comparison with PTZ group from 50% to 0%. Conclusion: PEA injection with Ganaxolone increased the anticonvulsive effects of Ganaxolone, and reduced mortality due to seizures.

Keywords

• anandamide
• endocannabinoid
• epilepsy
• neurosteroid