In Vitro Anticonvulsant Action of 2-Arachidonyl Glycerol

Previous studies had shown that the exogenous cannabinoids can induce anticonvulsion, which was believed to be mediated through the activation of central cannabinoid Type 1 receptors. Moreover, the endogenous cannabinoid anandamide has shown anticonvulsant properties in the in vitro preparations. The current study used 27 adult Sprague-Dawley rats to investigate the effects of another endogenously occurring cannabinoid called 2-arachidonyl glycerol on epileptiform activity induced by picrotoxin. Extracellular recordings were made from the pyramidal cell layer of the CA1 region of hippocampal slices maintained in an interface type recording chamber. Stimulation was performed by using single pulses. It evoked population spikes of approximately equal amplitude. Using single pulse stimulation, perfusion of 500 nM picrotoxin caused an 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, 2-AG reduced the amplitude of the population spikes, 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 2-AG. The current results showed that 2-AG caused anticonvulsion in the in vitro preparations. The results will open avenues for cannabinoid receptors as possible future therapeutic targets.