期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：16
页码：6222-6225
DOI：10.1073/pnas.0401479101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mice housed in social isolation exhibit a decreased response to {gamma}-aminobutyric acid-mimetic drugs [i.e., pentobarbital (PTB)] associated with a down-regulation of telencephalic allopregnanolone (Allo) levels. In these mice, the PTB-induced loss of righting reflex is greatly reduced. Fluoxetine (FLX) and norfluoxetine (NFLX) stereospecifically reverse the effect of social isolation on the PTB-induced loss of righting reflex and on the decrease of telencephalic Allo content. The S-isomers of FLX and NFLX are 2- and 7-fold more potent, respectively, than their respective R-isomers. The EC50s of FLX and NFLX required to normalize brain Allo content and PTB action are 10-50 times lower than the IC50s required for selective serotonin reuptake inhibitor activity. We conclude that normalization of PTB action elicited by the S-isomers of FLX and NFLX is related to the reversal of the down-regulation of brain Allo content and is independent of selective serotonin reuptake inhibitor activity.
