The effect of chronic caffeine intake on pentylenetetrazole (PTZ)-induced seizure threshold and nitric oxide metabolites in mice

Long-term caffeine intake decreases seizure susceptibility and has protective effect. This protective effect of caffeine may be due to the blockade of A2A adenosine receptors. Considering that activation of adenosine A2A receptors elevates nitric oxide production, the aim of the present study was to investigate the effect of chronic caffeine intake on the pentylenetetrazole (PTZ)-induced seizure threshold and measurement of nitric oxide metabolites levels in mice. In this study, NMRI male mice (weighing 25-30 g) were divided into 3 groups including one control and two experimental groups (n=9 in each group). PTZ- induced clonic seizure was measured following oral intake of caffeine in experimental groups (100 and 300 mg/L in the drinking water) or only tap water in the control group for 90 days. Measurement of nitric oxide metabolites in the brain tissues was done at the end of the experiments using the Greiss method. The chronic caffeine intake at concentrations of 100 and 300 mg/L in the drinking water for 90 days did not change the seizure threshold. On the other hand, both concentrations of caffeine significantly decreased nitric oxide metabolites levels compared to the control group (P<0.05). The results of this study confirmed and extended previous studies that chronic caffeine intake has no effect on seizure. Reduced levels of nitric oxide metabolites and resultant decreased neuronal excitability may be the main protective mechanism of the chronic caffeine intake. Blockade of the A2A adenosine receptors following the chronic caffeine intake may be involved in decreased levels of nitric oxide metabolites.