Effect of acute caffeine administration on PTZ-induced seizure threshold in mice: Involvement of adenosine receptors and NO-cGMP signaling pathway

Esmaili, Z. and Heydari, A. (2019) Effect of acute caffeine administration on PTZ-induced seizure threshold in mice: Involvement of adenosine receptors and NO-cGMP signaling pathway. Epilepsy Research, 149. pp. 1-8.

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Abstract

Abstract Purpose: Caffeine 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. Methods: NMRI male mice (25–30 g) received caffeine (5, 50, and 100 mg/kg) alone, whereas 8-CPT (1 and 5 mg/kg, a selective A1Rs antagonist), SCH-442416 (5 and 10 mg/kg, a selective A2ARs antagonist) or sildenafil (5 and 10 mg/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. Results: When administrated alone, caffeine (5 and 50 mg/kg) and 8-CPT (1 and 5 mg/kg) significantly decreased seizure threshold, while 100 mg/kg of caffeine, SCH-442416 or sildenafil did not change it. Only pre-treatment with SCH-442416 (5 and 10 mg/kg) or sildenafil (5 and 10 mg/kg) before 100 mg/kg of caffeine significantly decreased seizure threshold. Moreover, NOx levels significantly decreased following alone administration of caffeine (100 mg/kg) or 8-CPT (5 mg/kg). Conclusion: The results of present study showed that 5 and 50 mg/kg of caffeine had a proconvulsant effect but caffeine at a dose of 100 mg/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. Keywords: Seizure Caffeine Nitric oxide Adenosine receptors Pentylenetetrazole

Item Type: Article
Additional Information: cited By 0
Subjects: Neuroscience
Divisions: Faculty of Medicine > Basic Sciences > Department of physiology
Depositing User: ART . editor
Date Deposited: 10 Feb 2019 15:37
Last Modified: 10 Feb 2019 15:37
URI: http://eprints.kaums.ac.ir/id/eprint/3468

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