Epilepsy Research | 2019
Effect of acute caffeine administration on PTZ-induced seizure threshold in mice: Involvement of adenosine receptors and NO-cGMP signaling pathway
Abstract
PURPOSE\nCaffeine is a non-selective antagonist of A1 and A2A adenosine receptors (ARs). In this regard, nitric oxide (NO) is partly involved in the central effects of caffeine. In this study, we examined the effect of acute caffeine administration on pentylenetetrazole (PTZ)-induced seizure threshold by focusing on A1Rs, A2ARs, and NO-cGMP signaling pathway.\n\n\nMETHODS\nNMRI male mice (25-30\u2009g) received caffeine (5, 50, and 100\u2009mg/kg) alone, whereas 8-CPT (1 and 5\u2009mg/kg, a selective A1Rs antagonist), SCH-442416 (5 and 10\u2009mg/kg, a selective A2ARs antagonist) or sildenafil (5 and 10\u2009mg/kg, a phosphodiesterase 5 inhibitor) were administrated alone or as pre-treatment before caffeine. Seizure threshold was assessed by intravenous infusion of PTZ. Nitric oxide metabolites (NOx) were measured with the Griess method.\n\n\nRESULTS\nWhen administrated alone, caffeine (5 and 50\u2009mg/kg) and 8-CPT (1 and 5\u2009mg/kg) significantly decreased seizure threshold, while 100\u2009mg/kg of caffeine, SCH-442416 or sildenafil did not change it. Only pre-treatment with SCH-442416 (5 and 10\u2009mg/kg) or sildenafil (5 and 10\u2009mg/kg) before 100\u2009mg/kg of caffeine significantly decreased seizure threshold. Moreover, NOx levels significantly decreased following alone administration of caffeine (100\u2009mg/kg) or 8-CPT (5\u2009mg/kg).\n\n\nCONCLUSION\nThe results of present study showed that 5 and 50\u2009mg/kg of caffeine had a proconvulsant effect but caffeine at a dose of 100\u2009mg/kg had no effect on seizure threshold. In addition, it seems that the effect caffeine on seizure threshold is partly mediated through ARs or modulation of the NO-cGMP signaling pathway.