2-Arachidonoylglycerol Enrichment Reduced Epileptiform Activity of the Rat Hippocampus Induced with Pentylenetetrazol

Background & Objective: 2-arachidonoylglycerol (2-AG) and anandamide (AEA) are two major endocannabinoids. Using inhibitors of the enzymatic pathways involved in the elimination of 2-AG and AEA as well as synthetic 2-AG, we examined the effectiveness of these endocannabinoids on epileptiform activity induced in Wistar rats by pentylenetetrazol (PTZ). Materials & Methods: Adult male Wistar rats were used in this study. Epileptiform activity was induced in adult male Wistar rats by PTZ injection (20 mg/kg, i.p.). To inhibit 2-AG degradation WWL70 and JJKK048 (JJKK048: 1 mg/kg, WWL70: 5 mg/kg, i.p.) were used. To inhibit AEA elimination, URB597 and LY2183240 (URB597: 1 mg/kg, LY2183240: 2.5 mg/kg, i.p.) were used. Synthetic 2-AG was also examined (1 mg/kg, i.p.) before the PTZ injection. All drugs were dissolved in DMSO as vehicle and injected (i.p.) 15 minutes before the PTZ injection. Latency to onset and duration of the epileptiform activity were considered for statistical analysis. Results: Injection of (JJKK048+WWL70) before the PTZ significantly increased latency to onset of the epileptiform activity (P<0.01), while reduced duration of the epileptiform activity in comparison to the vehicle (P<0.05). In addition, 2-AG administration significantly increased latency to onset of the epileptiform activity (P<0.05) and reduced duration of the epileptiform activity in comparison to the vehicle (P<0.01). However, these indexes did not show significant changes when URB597+LY2183240 were injected before the PTZ (P>0.05). Conclusion: It seems increased level of 2-AG but not AEA, effectively decreases PTZ induced epileptiform activity of the hippocampus.