Frye C A, Scalise T J, Bayon L E
Department of Psychology, Connecticut College, New London 06320, USA.
J Neuroendocrinol. 1998 Apr;10(4):291-6. doi: 10.1046/j.1365-2826.1998.00202.x.
The purpose of the present study was to examine seizure activity during reduced 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) production. Ovariectomized Long-Evans rats were stereotaxically implanted with bipolar electrodes above the perforant pathway; silastic implants filled with estradiol-17-benzoate (EB) and progesterone were inserted subcutaneously to mimic diestrus. Estrus was then induced in half of these animals by injection of EB (30 microg) and progesterone (2.5 mg), 48 and 4 h, respectively, prior to perforant pathway stimulation. Half of the estrous and diestrous rats also received a 5alpha-reductase inhibitor, finasteride (50 mg/kg), 6 h prior to perforant pathway stimulation. The estrous condition was associated with reduced number and duration of partial seizures, improved performance on a Morris water maze recovery of function test, reduced neuronal loss in the hilar region of the hippocampus, and elevated central and plasma 3alpha,5alpha-THP, compared to estrus+finasteride, diestrus+vehicle and diestrus+finasteride conditions, which did not differ from each another. These data suggest antiseizure effects of estrus may be caused, in part, by the action of 3alpha,5alpha-THP and that the precipitous decline in 3alpha,5alpha-THP may restore seizure threshold to control levels.
本研究的目的是检测在5α-孕烷-3α-醇-20-酮（3α,5α-四氢孕酮）生成减少期间的癫痫活动。对去卵巢的Long-Evans大鼠进行立体定位，在穿通通路上方植入双极电极；皮下插入填充有雌二醇-17-苯甲酸酯（EB）和孕酮的硅橡胶植入物以模拟动情间期。然后在这些动物中的一半中，分别在穿通通路刺激前48小时和4小时注射EB（30微克）和孕酮（2.5毫克）来诱导发情。一半的发情期和动情间期大鼠在穿通通路刺激前6小时还接受了5α-还原酶抑制剂非那雄胺（50毫克/千克）。与发情期+非那雄胺、动情间期+赋形剂和动情间期+非那雄胺组相比，发情期与部分癫痫发作的次数和持续时间减少、在莫里斯水迷宫功能恢复测试中的表现改善、海马齿状回区域神经元损失减少以及中枢和血浆3α,5α-四氢孕酮升高有关，而后三组之间无差异。这些数据表明发情期的抗癫痫作用可能部分由3α,5α-四氢孕酮的作用引起，并且3α,5α-四氢孕酮的急剧下降可能使癫痫阈值恢复到对照水平。
