Haloperidol, spiperone, pimozide and aripiprazole reduce intracellular dopamine content in PC12 cells and rat mesencephalic cultures: Implication of inhibition of vesicular transport.
Haloperidol, spiperone, pimozide and aripiprazole reduce intracellular dopamine content in PC12 cells and rat mesencephalic cultures: Implication of inhibition of vesicular transport.
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DOI：
10.1016/j.ejphar.2010.04.043
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发表时间：
2010-08
影响因子：
5
通讯作者：
Takaaki Matsuo;Yasuhiko Izumi;Seiko Wakita;T. Kume;Yuki Takada‐Takatori;H. Sawada;A. Akaike
中科院分区：
文献类型：
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作者：
Takaaki Matsuo;Yasuhiko Izumi;Seiko Wakita;T. Kume;Yuki Takada‐Takatori;H. Sawada;A. Akaike
越来越多的证据表明，抗精神病药物影响多巴胺能神经元的多巴胺释放，但确切的机制尚未完全了解。此外，关于抗精神病药物对细胞内多巴胺含量影响的研究较少。本研究观察了8种抗精神病药物对PC12细胞多巴胺释放及细胞内多巴胺含量的影响。氟哌啶醇，螺哌隆，匹莫齐特，阿立哌唑和利培酮预处理显着抑制高钾诱发的多巴胺释放。相比之下，氯丙嗪预处理轻微增加高钾诱发的多巴胺释放，而舒必利和奥氮平预处理没有影响。氟哌啶醇、螺哌隆、匹莫齐特、氯丙嗪、阿立哌唑和奥氮平诱发多巴胺释放，而舒必利和利培酮则无此作用。此外，氟哌啶醇、螺哌隆、匹莫齐特、阿立哌唑和利培酮以浓度依赖性方式降低细胞内多巴胺含量。这些结果表明，减少高钾诱发的多巴胺释放的抗精神病药物预处理的结果从减少囊泡多巴胺含量。8种抗精神病药物治疗不影响总酪氨酸羟化酶或磷酸化酪氨酸羟化酶的表达。相反，氟哌啶醇，螺哌隆，匹莫齐特和阿立哌唑以及利血平短暂增加多巴胺代谢物的细胞外水平。此外，氟哌啶醇、螺哌隆、匹莫齐特、阿立哌唑和利培酮减少囊泡[3H]多巴胺转运。这些结果表明，氟哌啶醇、螺哌隆、匹莫齐特和阿立哌唑对囊泡多巴胺转运的抑制导致囊泡多巴胺含量降低。
Accumulating evidence suggests that antipsychotics affect dopamine release from dopaminergic neurons, but the precise mechanisms are not fully understood. Besides, there are few studies on the effects of antipsychotics on intracellular dopamine content. In this study, the effects of 8 antipsychotics on dopamine release and intracellular dopamine content in PC12 cells were investigated. Pretreatment with haloperidol, spiperone, pimozide, aripiprazole and risperidone markedly inhibited high potassium-evoked dopamine release. By contrast, pretreatment with chlorpromazine slightly increased high potassium-evoked dopamine release, while pretreatment with sulpiride and olanzapine had no effect. Haloperidol, spiperone, pimozide, chlorpromazine, aripiprazole and olanzapine evoked dopamine release, while sulpiride and risperidone had no effect. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced intracellular dopamine content in a concentration-dependent manner. These results suggest that the reduction in high potassium-evoked dopamine release by pretreatment with antipsychotics results from the reduction in vesicular dopamine content. Treatment with the 8 antipsychotics did not affect the expression of total or phosphorylated tyrosine hydroxylase. Instead, haloperidol, spiperone, pimozide and aripiprazole as well as reserpine transiently increased extracellular levels of dopamine metabolites. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced vesicular [3H]dopamine transport. These results suggest that the inhibition of vesicular dopamine transport by haloperidol, spiperone, pimozide and aripiprazole results in a reduction in vesicular dopamine content.