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It has been proved that kindling model of amygdala is sensitive to estradiol because the latter accelerates the overall rate of kindling. However the effect of estrogen on the seizure process has not been investigated. In this study fully kindled male rats were treated with different doses (10, 30, and 50 µg/kg, i.p.) of estradiol benzoate (EB) daily and such kindling parameters as seizure stage (SS), after-discharge duration (ADD) and stage 5 duration (S5D) were recorded 15 and 180 min and every 24 h following EB injection for a period of 96 h. While EB at a dose of 10 µg/kg failed to produce a significant effect, but its administration at doses of 30 and 50 µg/kg induced a triphasic effect on seizure parameters. In this regard an initial rapid increment of ADD (after 15 min) was followed by a significant decrease of all parameters after 48 h and then a significant increase in S5D after 96 h was observed. In addition, pretreatment with tamoxifen citrate (TAM) at a dose of 3 mg/kg inhibited the effects of EB (30 µg/kg) for 72 h and pretreatment with TAM at a dose of 10 mg/kg blocked only the inhibitory phase of EB effects after 48 h. Also treatment with the same dose of TAM alone induced a profile similar to EB treatment. These results may suggest that estradiol treatment both increases and decreases kindling parameters in a time- and dose-dependent manner in male rats. These effects probably manifest themselves in genomic and non-genomic forms. Moreover the tamoxifen effects alone could be attributed to its partial agonistic activity on the estrogen receptors.

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