Effects of dietary nitrate or nitrite supplementation on inhibitory avoidance task and pentylenetetrazole-induced clonic seizure threshold in mice

Introduction: The nitrate-nitrite-nitric oxide (NO) is considered a possible alternative pathway for NO production. Consequently, this research aimed to assess how adding dietary nitrate or nitrite affects the inhibitory avoidance task, the threshold for clonic seizures induced by pentylenetetrazole (PTZ), and levels of nitric oxide metabolites (NOx) in mice. Methods: In this research, 40 male NMRI mice were used, with 8 mice in each of the five groups including control and four experimental groups (given 50 or 100 mg/l nitrate or nitrite in drinking water for 21 days). The mice’s memory retention was assessed through the step-down passive avoidance test, while their locomotor activity was measured using the open-field apparatus. The seizure threshold was determined by administering PTZ through intravenous infusion. Additionally, the levels of NOx in the brain tissue were quantified using the Griess method. Results: Supplementation with either nitrate or nitrite at a concentration of 100 mg/L resulted in a significant increase in the step-down passive avoidance latency compared to the control group (P 0.01). Only nitrate at a concentration of 100 mg/L significantly increased the threshold for PTZ-induced clonic seizures (P 0.001). The levels of NOx were significantly elevated in all groups that received nitrate or nitrite at concentrations of 50 and 100 mg/L (P 0.05). Conclusion: We conclude that the nitrate-nitrite-NO pathway is partly involved in the memory-improving effects of nitrate or nitrite and the increase of PTZ-induced clonic seizure threshold following nitrate supplementation.