Inhibitory effects of chronic administration of vitamin D 3 on pentylenetetrazole-induced seizures in mice.

Vitamin D3 as a neuroactive steroid hormone plays an important role in the nervous system. Recent clinical and experimental studies have shown an association between vitamin D-related disorders and epilepsy. Therefore, this study was designed to examine the effects of chronic administration of vitamin D3 on pentylenetetrazole (PTZ)-induced seizure in mice. This interventional study was conducted on 120 mice in 12 groups. Two control groups acutely and chronically received a mixture of almond oil and paraffin; three groups were acutely given vitamin D3 at doses of 2000, 4000 and 6000 IU/kg; three groups chronically received vitamin D3 with similar doses for two weeks and two groups chronically and acutely received a sub-effective dose of vitamin D3 and diazepam. Slow intravenous infusion of PTZ (5 mg/mL) was performed at a constant rate (0.3 mL/min) via an infusion pump to induce clonic and tonic seizures. Acute injection of different concentrations of vitamin D3 (2000, 4000 and 6000 IU/kg i.p.) did not significantly increase a seizure threshold. However, a seizure threshold in the groups chronically treated with 4000, and 6000 IU/kg of vitamin D3 was significantly higher than that in the control group (P < 0.001). Moreover, a combination of the sub-effective dose of vitamin D3 (2000 IU/kg) and diazepam (0.1 mg/kg) significantly increased seizure threshold. Our findings suggest that administration of vitamin D supplement can be considered as a potential add-on treatment in seizure and due to the vitamin D deficiency results from the long-term use of most anti-seizure drugs, this supplementation becomes more important.