Decreased pallidal GABA following reverse microdialysis with clozapine, but not haloperidol.
Decreased pallidal GABA following reverse microdialysis with clozapine, but not haloperidol.
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使用氯氮平而非氟哌啶醇进行反向微透析后，苍白球 GABA 减少。
DOI：
10.1097/00001756-200112040-00010
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发表时间：
2001
期刊：
影响因子：
1.7
通讯作者：
Berglind,WJ
中科院分区：
文献类型：
--
作者：
See,RE;Berglind,WJ
纹状体类GABA的变化被认为在抗精神病药物（APDs）产生的运动副作用中起重要作用。在本研究中，我们测量了大鼠苍白球（GP）的细胞外GABA。GABA的释放部分依赖于冲动和ca2 +，这可以通过河豚毒素（TTX）或去除ca2 +后流出量的减少来证明。此外，高K+(100 mM KCl)刺激显著增加GABA释放。非典型APD的反透析，氯氮平（1-100 μM），产生细胞外GABA的浓度依赖性降低。而典型APD氟哌啶醇（1 ~ 100 μM）对GABA水平无显著影响。这些结果表明氯氮平在GP中有直接作用，而氟哌啶醇的作用很可能是通过其在纹状体中的作用介导的。氯氮平引起的白斑GABA减少可能是其低运动副作用的原因。
Changes in striatopallidal GABA are believed to play a significant role in the motor side effects produced by antipsychotic drugs (APDs). In the current study, we measured extracellular GABA in the globus pallidus (GP) of rats. GABA release was partially impulse-and Ca 2+-dependent, as evidenced by decreased efflux following tetrodotoxin (TTX) or removal of Ca 2+. In addition, GABA release was significantly increased by high K+(100 mM KCl) stimulation. Reverse dialysis of the atypical APD, clozapine (1–100 μM), produced a concentration dependent decrease in extracellular GABA. In contrast, the typical APD, haloperidol (1–100 μM), had no significant effect on GABA levels. These results suggest that clozapine has direct actions within the GP, while the effects of haloperidol are most likely mediated through its effects in the striatum. The clozapine-induced decrease in pallidal GABA may account for its low motor side effect liability.