ANXIOLYTIC EFFECTS OF 3A-HYDROXY-5A[BETA]-PREGNAN-20-ONE - ENDOGENOUS METABOLITES OF PROGESTERONE THAT ARE ACTIVE AT THE GABA-A RECEPTOR
ANXIOLYTIC EFFECTS OF 3A-HYDROXY-5A[BETA]-PREGNAN-20-ONE - ENDOGENOUS METABOLITES OF PROGESTERONE THAT ARE ACTIVE AT THE GABA-A RECEPTOR
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DOI：
10.1016/0006-8993(91)90761-j
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发表时间：
1991-10-04
期刊：
影响因子：
2.9
通讯作者：
KELLOGG, CK
中科院分区：
文献类型：
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作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
在成年雌性大鼠中评估了侧脑室注射孕酮还原代谢物对自发活动和高架十字迷宫探索的影响。别孕烯醇酮（3-α-羟基-5-α-葡聚糖-20-酮; 1.25、5.0和10 μ g）和孕烯醇酮（3-α-羟基-5-β-葡聚糖-20-酮; 2.5、5.0和10 μ g）引起抗焦虑作用，并且在最高测试剂量下，别孕烯醇酮导致镇静。相比之下，别孕烯醇酮的3-β-羟基-差向异构体在任一行为范例中都没有影响。对孕烷醇酮的抗焦虑反应被印防己毒素（0.75 mg/kg，腹腔注射）阻断，剂量本身不影响十字迷宫中的行为。这些数据表明，孕酮的3-α-羟基代谢物的抗焦虑作用是由脑GABA（A）受体以立体特异性方式介导的，并且与这些类固醇作为GABA（A）受体的有效调节剂的充分记录的体外作用一致。
The effects of intracerebroventricular administration of reduced metabolites of progesterone on locomotor activity and on exploration in the elevated plus-maze were assessed in adult female rats. Allopregnanolone (3-alpha-hydroxy-5-alpha-pregnan-20-one; 1.25, 5.0, and 10-mu-u-g) and pregnanolone (3-alpha-hydroxy-5-beta-pregnan-20-one; 2.5, 5.0, and 10-mu-ug) elicited anxiolytic effects and, at the highest dose tested, allopregnanolone resulted in sedation. In contrast, the 3-beta-hydroxy-epimer of allopregnanolone was without effect in either behavioral paradigm. The anxiolytic response to pregnanolone was blocked by picrotoxin (0.75 mg/kg, i.p.), a dose that by itself did not affect behavior in the plus-maze. These data suggest that the anxiolytic effect of 3-alpha-hydroxy metabolites of progesterone is mediated by brain GABA(A) receptors in a stereospecific manner, and are in good agreement with the well-documented in vitro effects of these steroids as potent modulators of the GABA(A) receptor.