study of anticonvulsant effect of some steroids on induced seizures in adult male mice

ABSTRACT

Hormones influence brain functions throughout life and might alter seizures susceptibility by affecting neuronal excitability. Alterations in gamma amino butyric acid [GABA,] ergic neurotransmission are associated with seizures disorders and consequently much of antiepileptic therapy is directed towards the GABA A receptor complex. In humans, seizures patterns are affected by some factors such as the onset of puberty, pregnancy and stress suggesting that there is an underlying hormonal component. the present study was conducted to evaluate the anticonvulsant effect and the possible mechanism of action of some steroid hormones. Progesterone, deoxycorticosterone [DOC] and dehydroepiandrosterone [DHEA] in experimentally induced seizures in male mice. This study was carried out on adult albino male mice weighing 24-26gm and included two experiments experiment I, in which two models of seizures were used; pentylenetetrazol [PTZ] model and maximal electro-convulsive shock seizures [MES] model. In each model, the animals were divided into 5 groups. The first group was kept as a control group and each of the other 4 groups was subdivided into 3 subgroups, 20 animal each. The treated groups included diazepam, progesterone, DOC and DHEA treated groups at different doses. In PTZ model, PTZ was given in a dose of 70 mg/kg by intraperifoneal [i.p.] injection to induce chemoconvulsant seizures while in MES model, the animal received a stimulus train of electric current 25 mA, 50 Hz through the brain via ear electric clip. Diazepam and hormones were given 30 mm prior to PTZ injection or MES induced seizures. Experiment II in which bicuculline, a GABA A receptor antagonist was used in a dose of 1 mg/kg subcutaneously [s.c] 15 mm prior to administration of hormones. The ictal activity [latency, duration of myoclonic seizures and percent of protection against seizures and mortality] was recorded in either experiment. It was observed that progesterone suppressed PTZ induced seizures where it significantly [P<0. 001] prolonged the latency and shortened the duration of myoclonic seizures as compared to control with median effective dose [ED 50] of about 20 mg/kg s.c. The protection against seizures was 60, 70 and 75% and against mortality was 100%. Also, DOC administration exhibited a potent significant anticonvulsant activity in PTZ model in comparison to control and nearly equal to diazepam treatment. The ED 50 of DOC was 5 mg/kg and complete protection against seizures and mortality was observed at 20 and 80 mg/kg. In MES model, administration of progesterone at.20 and 80 mg/kg induced no significant anticonvulsant effect and ED 50 war observed at a higher dose [160 mg/kg]. Treatment with DOC 5 mg/kg produced no anticonvulsant activity, ED 50 was 20 mg/kg and complete protection against seizures was reached at 80 mg/kg. Both in PTZ and MES model, diazepam at the all tested doses induced a significant anhiconvulsant effect, while DHEA lacked any anticonvulsant activity, even it has a convulsant effect. Pretreatment with. bicuculline prior to progesterone and DOC administration caused a significant reversal of the anticonvulsant activity of these hormones. These findings indicate that the steroid hormones; progesterone and DOC have a broad spectrum anticonvulsant activity in animal seizures models [especially PTZ model] mediated by GABA A receptor modulation. Therefore, they might be involved in the modification of seizures frequency and epilepsy and might have a clinical importance in the future treatment of seizures disorders in conjunction with the usual antiepileptic drugs. On the other hand, DHEA has no anti convulsant effect