The CB1 cannabinoid receptors involvement in anti-epileptic effect of safranal on penicillin-induced epileptiform activity in rats.

Neuroprotective effects for natural products are supported by several studies. In this regard, safranal, a constitute of saffron, has the potential to exert beneficial effects in neuro-logical disorders such as Parkinson's disease, epilepsy, stroke, multiple sclerosis and Alzheimer's disease. Here, we investigated the effect of safranal on penicillin-induced epileptiform activity. Also, the effects of intracerebroventricular (ICV) microinjection of AM251 as a CB1-cannabinoid receptors antagonist to clarify the possible mechanism of safranal were evaluated. Epileptiform activity was induced by intra-cortical administration of penicillin (300 IU, 1.50 μL) in urethane-anesthetized rats. Electrocorticographic recordings were used to analyze the frequency and amplitude of spike waves. Intraperitoneal injections of safranal at doses of 1.00 and 4.00 mg kg^-1 significantly reduced both the number and amplitude of spike waves. The ICV microinjection of AM251 (0.50 μg 2.00 μL^-1) significantly increased the frequency and amplitude of spike waves. In addition, the anti-epileptic effect induced by administration of safranal at a dose of 4.00 mg kg^-1 was partially prevented by ICV microinjection of 0.50 μg 2.00 μL^-1 of AM251. The results showed anti-epileptiform activities for safranal. Central CB1 cannabinergic receptors might be involved in the anti-epileptiform activity of safranal.