Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.

Sadri Vakili G; Johnson DW; Janis GC; Gibbs TT; Pierce RC; Farb DH

首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >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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Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.

机译：抑制NMDA诱导的纹状体多巴胺的释放和神经活性类固醇3alpha-羟基-5beta-pregnan-20-半琥珀酸酯的行为激活。

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Our laboratory has previously shown that the synthetic neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate (3alpha5betaHS) is a negative modulator of NMDA receptors in vitro. Similarly, 3alpha5betaHS exhibits rapid sedative, analgesic, anticonvulsive, and neuroprotective effects in vivo. Here we report a study designed to investigate whether a negatively charged neuroactive steroid, 3alpha5betaHS, modulates the action of NMDA receptors in vivo. Our results indicate that peripherally administered 3alpha5betaHS 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 3alpha5betaHS and the NMDA-induced increase in extracellular dopamine in the striatum was also attenuated by both systemically administered and intrastriatally administered (by in vivo microdialysis) 3alpha5betaHS. These data indicate that 3alpha5betaHS acts through striatal NMDA receptors in 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.

机译：我们的实验室以前已经表明，合成的神经活性类固醇3alpha-羟基-5beta-pregnan-20-一丁二酸酯（3alpha5betaHS）在体外是NMDA受体的负调节剂。同样，3alpha5betaHS在体内表现出快速的镇静，镇痛，抗惊厥和神经保护作用。在这里，我们报告了一项旨在调查带负电荷的神经活性类固醇3alpha5betaHS是否在体内调节NMDA受体作用的研究。我们的结果表明，外围给药的3alpha5betaHS进入中枢神经系统并抑制NMDA介导的运动活性和大鼠纹状体中的多巴胺释放。全身给药3alpha5betaHS可阻止由纹状体内注射NMDA诱导的运动活动的增加，并且全身给药和纹状体内给药（通过体内微透析）3alpha5betaHS均可抑制NMDA诱导的纹状体中细胞外多巴胺的增加。这些数据表明3alpha5betaHS在体内通过纹状体NMDA受体起作用。综合起来，这些结果表明，神经活性类固醇可能被证明可有效治疗中脑多巴胺系统中过度刺激NMDA受体的神经和精神疾病。

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《Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry》 |2003年第1期|共10页
作者
Sadri Vakili G; Johnson DW; Janis GC; Gibbs TT; Pierce RC; Farb DH;
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正文语种 eng
中图分类生物化学;
关键词
3-hydroxy-5-beta-pregnan-20-one hemisuccinate; N-Methylaspartate; Dopamine; N-甲基天冬氨酸; 多巴胺; 受体; N-甲基-D-天冬氨酸;

机译：3-hydroxy-5-beta-pregnan-20-one hemisuccinate;N-Methylaspartate;Dopamine;N-甲基天冬氨酸;多巴胺;受体;N-甲基-D-天冬氨酸;

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1. Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate. [J] . Sadri Vakili G, Johnson DW, Janis GC, Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry . 2003,第1期

机译：抑制NMDA诱导的纹状体多巴胺的释放和神经活性类固醇3alpha-羟基-5beta-pregnan-20-半琥珀酸酯的行为激活。
2. Inhibition of striatal dopamine release by CB1 receptor activation requires nonsynaptic communication involving GABA, H(2)O(2), and K(ATP) channels. [J] . Sidlo Z, Reggio PH, Rice ME Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry . 2008,第1a2期

机译：通过CB1受体激活抑制纹状体多巴胺释放需要涉及GABA，H（2）O（2）和K（ATP）通道的非突触通讯。
3. Activation of ATP-sensitive K+ (K(ATP)) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release. [J] . Avshalumov MV, Rice ME Proceedings of the National Academy of Sciences of the United States of America . 2003,第20期

机译：H2O2对ATP敏感K +（K（ATP））通道的激活是谷氨酸依赖性抑制纹状体多巴胺释放的基础。
4. Inhibition of T-type Calcium Current in the Reticular Thalamic Nucleus by a Novel Neuroactive Steroid [C] . PAVLE M. JOKSOVIC, DOUGLAS F. COVEY, SLOBODAN M. TODOROVIC International Conference on Neuroprotective Agents: Clinical and Experimental Aspects . 2007

机译：一种新型神经活性类固醇抑制网状丘脑核中的T型钙电流
5. Characterization of the behavioral effects of the neuroactive steroid pregnanolone on schedule-controlled behavior in DBA/2J and C57BL/6J inbred mice. [D] . Shannon, Erin E. 2006

机译：在DBA / 2J和C57BL / 6J近交小鼠中，神经活性类固醇孕烷醇酮对日程控制行为的行为影响的表征。
6. Activation of ATP-sensitive K+ (KATP) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release [O] . Marat V. Avshalumov, Margaret E. Rice 2003

机译：H2O2激活ATP敏感性K +（KATP）通道是谷氨酸依赖性抑制纹状体多巴胺释放的基础
7. Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3α-hydroxy-5β-pregnan-20-one hemisuccinate [O] . G. Sadri-Vakili, D. W. Johnson, G. C. Janis, 2004

机译：NMDA诱导的纹状体多巴胺释放和神经活性类固醇3α-羟基-5β-PEALAN-20-一苏酸的行为活化的抑制作用

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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