Anticonvulsant action of anandamide in an in vitro model of epilepsy

OBJECTIVE: In both in vitro and in vivo models of epilepsy, cannabinoids had anti-convulsant properties, which have been shown to be mediated through activation of central cannabinoid type 1 receptors (CB1). The current study used 24 adult Sprague Dawley rats to investigate the effects of endogenously occurring cannabinoids (endocannabinoids) on epileptiform activity induced by picrotoxin.

METHODS: We carried out the study at King Fahad Medical Research Center, Jeddah, Kingdom of Saudi Arabia in September 2004. We made extracellular recordings from stratum pyramidale of the CA1 region of hippocampal slices maintained in a submersion type recording chamber. Stimulation with single pulses, evoked population spikes of approximately equal amplitude.

RESULTS: Using single pulse stimulation, perfusion of 0.5 uM picrotoxin caused a small increase in the amplitude of the first population spike, and caused epilepsy by introducing a second or multiple population spikes. In the presence of picrotoxin, anandamide reduced the amplitude of both the first population spike (PS1) and the second population spike (PS2), thus reducing the epilepsy. The CB1 receptor antagonist, AM281 (500 nM) had no effect on responses recorded in the presence of picrotoxin, but totally blocked the effect of subsequently perfused anandamide.

CONCLUSION: The results showed that anandamide caused an anti-convulsant effect. Furthermore, these results implicate the cannabinoid CB1 receptor as a major endogenous site of seizure modulation.