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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Cyclic withdrawal from endogenous and exogenous progesterone increases kainic acid and perforant pathway induced seizures.
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Cyclic withdrawal from endogenous and exogenous progesterone increases kainic acid and perforant pathway induced seizures.

机译：从内源性和外源性孕酮的周期性停药会增加海藻酸和穿孔途径诱发的癫痫发作。

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摘要

Antiseizure effects of progesterone (P) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha, 5alpha-THP) were investigated following continuous vs. discontinuous P exposure. In Experiments 1, 32 cycling Long-Evans rats were administered kainic acid (32 mg/kg SC), ictal behavior was examined, and plasma 3alpha,5alpha-THP levels were measured by radioimmunoassay. Proestrus/estrus rats showed less ictal activity and had elevated 3alpha,5alpha-THP levels prior to kainic acid compared to diestrus/metestrus subjects. In Experiment 2, 49 ovariectomized (ovx) rats were SC injected with estradiol benzoate (EB; 10 microg) and P (500 microg), to mimic estrus, or sesame oil vehicle (0.2 cc); all subjects were administered kainic acid. Rats tested with EB+P showed a reduced mean duration of full seizures and increased 3alpha,5alpha-THP, whereas those tested 24 h following EB+P had more tonic clonic seizures and lower 3alpha,5alpha-THP concentrations, comparable to ovx control animals. In Experiment 3, 49 ovx rats were stereotaxically implanted with bipolar electrodes into the perforant pathway. Prior to perforant pathway stimulation, rats received cholesterol or EB+P capsules for 1 month, continuously or intermittently. Irrespective of continuous or intermittent EB+P, the presence of progestins at the time of perforant pathway stimulation reduced partial seizure activity. Continuous EB+P capsules resulted in increased 3alpha,5alpha-THP levels compared to all other conditions, and less damage in the hilus of the hippocampus, compared to intermittent EB+P. These data confirm that P and 3alpha,5alpha-THP have antiseizure effects, and further suggest that repeated cycles of endogenous or exogenous P and/or 3alpha,5alpha-THP withdrawal influences seizure threshold and/or hippocampal integrity.
机译：在连续或不连续的P暴露后，研究了孕酮（P）及其代谢产物5alpha-pregnan-3alpha-ol-20-one（3alpha，5alpha-THP）的抗癫痫作用。在实验1中，对32只骑自行车的Long-Evans大鼠施用了海藻酸（32 mg / kg SC），检查了其发作行为，并通过放射免疫测定法测定了血浆3alpha，5alpha-THP水平。与发情期/发情期受试者相比，海藻酸前的发情期/发情期大鼠表现出较少的冰活动和升高的3alpha，5alpha-THP水平。在实验2中，对49只卵巢切除的（ovx）大鼠进行了SC注射，分别注射了雌二醇苯甲酸酯（EB; 10 microg）和P（500 microg），以模拟发情或芝麻油媒介物（0.2 cc）;所有受试者均施用海藻酸。与ovx对照动物相比，用EB + P测试的大鼠显示出完全癫痫发作的平均持续时间减少，并且3alpha，5alpha-THP升高，而在EB + P之后24小时测试的大鼠具有更高的强直阵挛性癫痫发作和更低的3alpha，5alpha-THP浓度。 。在实验3中，将49只ovx大鼠用双极电极立体定位植入穿孔通路。在穿孔途径刺激之前，大鼠连续或间歇接受胆固醇或EB + P胶囊1个月。不管连续或间歇性EB + P，穿孔途径刺激时孕激素的存在都会降低部分癫痫发作的活动。与间歇性EB + P相比，连续EB + P胶囊与所有其他条件相比，导致3alpha，5alpha-THP水平升高，对海马海带的损害较小。这些数据证实P和3alpha，5alpha-THP具有抗癫痫作用，并进一步表明内源性或外源性P和/或3alpha，5alpha-THP戒断的重复周期会影响癫痫发作阈值和/或海马完整性。

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