ANXIOLYTIC EFFECTS OF 3A-HYDROXY-5A[BETA]-PREGNAN-20-ONE - ENDOGENOUS METABOLITES OF PROGESTERONE THAT ARE ACTIVE AT THE GABA-A RECEPTOR

被引:405
|
作者
BITRAN, D
HILVERS, RJ
KELLOGG, CK
机构
[1] Department of Psychology, University of Rochester, Rochester
关键词
ALLOPREGNANOLONE; PREGNANOLONE; PICROTOXIN; PLUS-MAZE; ANXIETY; SEDATION; INTRACRANIAL ADMINISTRATION;
D O I
10.1016/0006-8993(91)90761-J
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:157 / 161
页数:5
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