Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.
Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.
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神经活性类固醇 3α-羟基-5β-孕-20-一半琥珀酸酯抑制 NMDA 诱导的纹状体多巴胺释放和行为激活。
DOI：
10.1046/j.1471-4159.2003.01814.x
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发表时间：
2003
影响因子：
4.7
通讯作者：
Farb,DH
中科院分区：
文献类型：
--
作者：
Sadri-Vakili,G;Johnson,DW;Janis,GC;Gibbs,TT;Pierce,RC;Farb,DH
Our laboratory has previously shown that the synthetic neuroactive steroid 3α‐hydroxy‐5β‐pregnan‐20‐one hemisuccinate (3α5βHS) is a negative modulator of NMDA receptorsin vitro. Similarly, 3α5βHS exhibits rapid sedative, analgesic, anticonvulsive, and neuroprotective effectsin vivo. Here we report a study designed to investigate whether a negatively charged neuroactive steroid, 3α5βHS, modulates the action of NMDA receptorsin vivo. Our results indicate that peripherally administered 3α5βHS enters the CNS and inhibits NMDA‐mediated motor activity and dopamine release in the rat striatum. The increase in motor activity induced by intrastriatal microinjection of NMDA was blocked by the systemic administration of 3α5βHS and the NMDA‐induced increase in extracellular dopamine in the striatum was also attenuated by both systemically administered and intrastriatally administered (byin vivomicrodialysis) 3α5βHS. These data indicate that 3α5βHS acts through striatal NMDA receptorsin vivo. When taken together, these results suggest that neuroactive steroids may prove to be effective in the treatment of neurological and psychiatric disorders involving over‐stimulation of NMDA receptors in the mesotelencephalic dopamine system.
