Effects of endocannabinoids in pentylenetetrazole induced seizures in mice

Aim: Pentylenetetrazole (PTZ) is an agent widely used for the assessment of putative anticonvulsant drugs and is supposed to induce repetitive firing of nerve fibers as well as shorten the refractory period. Anandamide is an endocannabinoid synthesized in neurons, excreted by depolarization and inactivated very quickly. Ethanol is a psychoactive substance which has an anti convulsive effect after acute application, although repeated administrations of high doses lead to proconvulsant actions. In order to explore whether endocannabinoids are effective in the treatment of epilepsy or not, we aimed to study the effect of anandamide on PTZ induced epileptic seizures in mice by determining which types of cannabinoid receptors are. Methods: In our small animal experimental model, thirty-two Swiss albino male mice weighing 25-35 g were used. During the study, the experimental animals were randomly divided into four groups as the control, anandamide, synthetic analogue of anandamide (WIN 55.212-2), and ethanol and the number of epileptic attacks, duration of the first epileptic attack, the total duration of the epileptic attacks and the latency time to the first attack after PTZ injection, mortality and the day of kindling development were compared in each group. Results: The mortality rate and seizure duration were significantly lower in all of the anandamide, WIN 55.212-2 and ethanol groups. After pre-PTZ injection of ethanol and anandamide, latency periods were significantly higher, without any difference between the groups. However, a similar relationship was not present between WIN 55.212-2 and ethanol. Conclusion: Our data showed that the antiepileptic effect of endocannabinoid anandamide observed was due to the its solvent, ethanol; however this effect was not found with its analogue WIN 55.212-2. Although both endocannabinoids resulted in interaction in the cannabinoid receptors, this difference may be the result of their different pharmacokinetics, metabolisms or degradation products and active metabolites.