The influence of ovariectomy on anti-convulsant effect of pioglitazone in mice

The anti-convulsant effects of pioglitazone in male animals have been reported in previous studies. Both clinical and animal studies demonstrated that ovarian hormones can influence seizure activity. Pioglitazone has direct effects on ovaries and changes the level of gonadal hormones. In the current study, we examined the influence of ovariectomy on seizure threshold in pioglitazone-treated female mice. Two models of intravenous and intraperitoneal pentylenetetrazole-induced clonic seizures were used to analyze the effect of pioglitazone in sham and ovariectomized female mice. Different doses of pioglitazone were administered orally for 10 days in different groups. We demonstrated that chronic administration of pioglitazone (10 and 20 mg/kg) increased clonic seizure threshold in intravenous pentylenetetrazole seizure model of female mice. We also indicated that chronic treatment with pioglitazone (10 and 20 mg/kg) increased clonic seizure latency in intraperitoneal pentylenetetrazole seizure model in female mice, while the incidence of tonic seizure and death remained unchanged. Ovariectomy abolished anti-seizure effect of pioglitazone in both seizure models of intravenous and intraperitoneal pentylenetetrazole. In conclusion, pioglitazone exerts anti-convulsant effect in both seizure models of intravenous and intraperitoneal pentylenetetrazole possibly through gonadal hormones of ovary in female mice.