Anticonvulsant action of anandamide in an in vitro model of epilepsy

Objectives: In both in vitro and in vivo models ofepilepsy, cannabinoids had anti-convulsant properties,which have been shown to be mediated throughactivation of central cannabinoid type 1 receptors (CB1).The current study used 24 adult Sprague Dawley rats toinvestigate the effects of endogenously occurringcannabinoids (endocannabinoids) on epileptiform activityinduced by picrotoxin.Methods: We carried out the study at King FahadMedical Research Center, Jeddah, Kingdom of SaudiArabia in September 2004. We made extracellularrecordings from stratum pyramidale of the CA1 region ofhippocampal slices maintained in a submersion typerecording chamber. Stimulation with single pulses,evoked population spikes of approximately equalamplitude.Results: Using single pulse stimulation, perfusion of0.5 ìM picrotoxin caused a small increase in theamplitude of the first population spike, and causedepilepsy by introducing a second or multiple populationspikes. In the presence of picrotoxin, anandamidereduced the amplitude of both the first population spike(PS1) and the second population spike (PS2), thusreducing the epilepsy. The CB1 receptor antagonist,AM281 (500 nM) had no effect on responses recorded inthe presence of picrotoxin, but totally blocked the effectof subsequently perfused anandamide.Conclusion: The results showed that anandamidecaused an anti-convulsant effect. Furthermore, theseresults implicate the cannabinoid CB1 receptor as a majorendogenous site of seizure modulation.