A Possible Non-genomic Epileptogenic Properties of Estradiol Attenuated by MK801 and DNQX in Amygdala Kindled Rats

Although the epileptogenic properties of estrogens have been widely demonstrated in several models and species, the mechanism(s) by which estrogens can acutely change seizure parameters including after discharge and seizure duration remain remains to be determined. In the present study, we examined the role of NMDA (N-methyl-D-aspartate), non-NMDA and estrogenic receptors in estradiol benzoate (EB) effects on kindled seizure parameters. Different groups of fully kindled male rats received either EB (30 μg /kg); EB plus MK801 (2 mg/kg, as NMDA antagonist); DNQX (7.5 mg/kg); tamoxifen (TAM, 0.1 mg/kg, as non-NMDA antagonist) or intra-amygdala injection of anisomycine (30 mmol/ml, a protein synthesis inhibitor). Kindled seizure parameters including after discharge duration (ADD) and stage 5 duration (S5D) were determined at 0.25 and 3 h post sesame oil (EB solvent) or EB treatment. While pretreatment with either MK801 or DNQXcould block the ADD prolongation induced by EB at 0.25 h, they had no effect on S5D prolongation at 3 h. Moreover, application of anisomycine or TAM had no effect on estradiol induced ADD and S5D prolongation. These results indicate that both NMDA and non-NMD A receptors could be involved in EB induced ADD prolongation. The observed short term non-estrogenic receptor or protein synthesis dependent effects of EB may provide a non-genomic mechanism for the stimulatory effects of the steroid on seizure activity.