Posible involvement of nitric oxide in anticonvulsant effects of citicoline on pentylenetetrazole and electroshock induced seizures in mice

Abstract

Cerebroneurovascular trauma is recognized as an important risk factor in the development of seizure and epilepsy. Administration of citicoline in these situations is a conventional therapeutic strategy, which combines neurovascular protection and repair effects. The aim of the present study is clarifying the effect of acute and sub-chronic citicoline administration on pentylenetetrazole (PTZ) and electroshock induced seizures in mice. Besides we examined the probable role of NO and its interaction with citicoline in seizure experiments. Male mice were received acute and sub-chronic regimens of different doses of citicoline (62.5, 125, 250 and 500 mg/kg) before the intravenous or intraperitoneal PTZ-induced seizures or electroshock. To clarify the probable role of NO, 7-nitroindazole (7-NI) (60 mg/kg) or aminoguanidine (AG) (100 mg/kg) were injected 5 min before citicoline in separate groups. The results revealed that neither acute nor sub-chronic treatment with citicoline could affect the seizures induced by intravenous or intraperitoneal PTZ, but in electroshock model, citicoline showed anti-epileptic properties. Co-administration of citicoline and selective nitric oxide synthase (NOS) inhibitors amplified the anticonvulsant effect of citicoline. The current results indicated that citicoline has anticonvulsant effects probably through the inhibition of NO.

Keywords: Citicoline; Electroshock; Mice; Neuroscience; Nitric oxide; Pentylenetetrazole; Seizures.

Figure 1

Effect of acute (A) and sub-chronic (B) treatment with different doses (125, 250 and 500 mg/Kg) of citicoline on the seizure thresholdin IV PTZ model. Data are presented as mean ± S.E.M.

Figure 2

Effect of acute treatment with different doses (125, 250 and 500 mg/Kg) of citicoline on myoclonic seizure latency (A) and clonic seizure latency (B) in IP PTZ model. Data are presented as mean ± S.E.M.

Figure 3

Effect of sub-chronic treatment with different doses (125, 250 and 500 mg/Kg) of citicoline on myoclonic seizure latency (A) and clonic seizure latency (B) in IP PTZ model. Data are presented as mean ± S.E.M.

Figure 4

Effect of acute and sub-chronic treatment with different doses (125, 250 and 500 mg/Kg) of citicoline on the duration of tonic hind-limb extension (THE). Data are presented as mean ± S.E.M. ∗∗p < 0.01 and ∗∗∗p < 0.001 compared with physiological saline group.

Figure 5

Effect of acute and sub-chronic treatment with 62.5 mg/kg citicoline in the presence of aminoguanidine (a selective iNOS inhibitor) (AG) or 7-nitroindazole (a selective nNOS inhibitor) (7-NI) on tonic hind-limb extension (THE) duration in electroshock model. Data are expressed as mean ± SEM. ∗p < 0.05 and ∗∗p < 0.01 compared with physiological saline group.