小鼠惊厥时孕烯醇酮及其硫酸盐对GABAA受体的调制作用

在建立稳定的红藻氨酸(KA)诱发小鼠惊厥模型的基础上,用放射配体受体结合分析法,研究孕烯醇酮(Pe)及其拮抗剂孕烯醇酮硫酸盐(Pes)对小鼠下丘脑、大脑皮层、海马和小脑四个脑区γ-氨基丁酸A(GABAA)受体的调制作用.结果显示,Pe能增加某些脑区3H-GABA与GABAA受体的结合量,下丘脑、海马和小脑差异显著(P＜0.05或P＜0.001),而大脑皮层差异不显著(P＞0.05).Pe对GABAA受体的调制作用能被印防己毒素(Pic)阻断,对KA的致惊效应具有抑制作用.Pes 能显著降低各脑区GABAA受体的结合量(P＜0.01或P＜0.001),对惊厥有促进作用.实验结果提示:孕烯醇酮具有明显的镇静和抗惊厥效应,并且可能是通过GABAA受体介导的.

MODULATION OF GABAA RECEPTORS BY PREGNENOLONE AND PREGNENOLONE SULFATE IN MOUSE BRAIN DURING CONVULSION

Recent investigation shows the regulation of GABA A receptor by neurosteroids in mammalian brain. Though progesterone can be used as psychotropic drug via its interaction with GABA A receptor,the role of pregnenolone (Pe) and pregnenolone sulfate (Pes) remains unclear. To further elucidated neurosteroids on the modulation of GABA A receptor, we investigated the effect of Pe and Pes on the 3H GABA binding to the GABA A receptors in hypothalamus,cerebral cortex, hippocampus and cerbellum in mice using a convulsion model induced by kainic acid. The results showed that Pe increased the binding of 3H GABA to the GABA A receptors in the tested brain areas. The increase of binding in the hypothalamus, hippocampus and cerebellum was significant (P <0 05 or P <0 001), but the inerese of binding in cerebral cortex was not significant ( P> 0 05). The modulation effect of Pe on GABA A receptors was blocked by picrotoxin, and consequently the kainic acid induced convulsion was inhibited. On the other hand, Pes markedly decreased the binding of the 3H GABA to GABA A receptors( P <0 01 or P <0 001) in all of the tested brain areas and enhanced the potency of kainic acid induced convulsive. These results suggest that Pe had marked sedative and anti convulsion effects, which were probably mediated by the GABA A receptors.