Proconvulsant effects of estriol, the third estrogen, in the mouse PTZ-kindling model

The effect of estriol, the third estrogen, was evaluated for its effect on pentylenetetrazole (PTZ)-kindling model of epileptogenesis in mice followed by evaluation on kindling-induced changes in cognitive and motor functions. Kindling was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks. The seizure severity during induction of kindling and percentage incidence of animals kindled at the end of 5 weeks was recorded. Motor function was assessed using a grip strength meter while spatial memory was assessed in a cross maze. Estriol (0.005 and 0.01 mg/kg i.p.) reduced the time for induction of kindling from 5 weeks to 3 and 2 weeks for male and female mice respectively and enhanced the percentage incidence of seizures. Clomiphene (0.9 mg/kg i.p.) delayed the development of kindling and produced anticonvulsant effects. It also partially reversed the proconvulsant effects of estriol. On grip strength test and spontaneous alternation behaviour, a significant decline was observed in kindled mice which was further reduced by pre-treatment with estriol. Both clomiphene and diazepam were unable to reverse the reduced GS of PTZ-kindled mice but enhanced the percentage alternation of such animals. The study shows that estriol has powerful proconvulsant effects. Its administration in hormone replacement therapy or other indications, thus, requires careful monitoring in patients susceptible to epileptic seizures. The anticonvulsant effects of clomiphene requires further investigations.