Effect of medroxyprogesterone on development of pentylenetetrazole-induced kindling in mice.Neuroscience. 2012 Apr 05; 207:283-7.N
In the present study, the effect of medroxyprogesterone (MPA) is 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. To explore whether the effects are mediated via progesterone receptors, a selective antagonist of progesterone (mifepristone, MIF) was also taken. 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 % incidence of animals kindled at the end of 5 weeks were recorded. The motor function was assessed using a grip strength meter, whereas spatial memory was assessed in a cross maze. MPA (5 and 10 mg/kg, i.p.) significantly reduced the seizure severity scores and produced a significant decrease in the incidence of animals kindled at the end of 5 weeks (P<0.01). A higher efficacy was observed against male mice as compared with females following MPA. MIF neither reduced nor delayed the development of PTZ-induced kindling in mice. Also, it couldn't reverse the antiepileptogenic effects of MPA. On grip strength test (GST) and spontaneous alternation behavior (SAB), a significant decline in GST and % alternation was observed in kindled mice which was reversed by pre-treatment with MPA. MIF, however, could reverse only the reduced % alternation and not grip strength (GS) in PTZ-kindled animals. The study shows that MPA has antiepileptogenic effects against development of PTZ-induced kindling in mice that may not be mediated via progesterone receptors.