Attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity by the novel selective dopamine D3-receptor partial agonist FAUC 329 predominantly in the nucleus accumbens of mice.
Attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity by the novel selective dopamine D3-receptor partial agonist FAUC 329 predominantly in the nucleus accumbens of mice.
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新型选择性多巴胺 D3 受体部分激动剂 FAUC 329 主要在小鼠伏核中减弱 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 神经毒性
DOI：
10.1016/s0006-2952(03)00451-9
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发表时间：
2003
影响因子：
5.8
通讯作者：
Ferger
中科院分区：
文献类型：
--
作者：
Boeckler;Bettinetti;Feldon;Gmeiner;Ferger
我们以前合成了一种新的多巴胺（DA）部分激动剂FAUC 329，具有高亲和力和选择性的DA D3受体。这是首次在帕金森病MPTP（1-甲基-4-苯基-1，2，3，6-四氢吡啶）小鼠模型中研究FAUC 329的保护作用的体内研究。成年雄性C57 bl/6小鼠在MPTP前30分钟注射FAUC 329（0、0.1、0.5、0.75或1 mg/kg）（2× 30 mg/kg，间隔4小时）。1周后，取中脑和纹状体组织进行DA及其代谢产物的HPLC测定，并对黑质腹侧被盖区和背侧被盖区DA转运蛋白阳性神经元进行免疫组织化学分析。FAUC 329以剂量依赖性方式显着减弱MPTP诱导的伏隔核DA减少（0.5、0.75和1 mg/kg）。FAUC 329（0.75mg/kg）部分保护背侧纹状体中的DA耗竭以及保护黑质背侧部中DA转运蛋白免疫反应性的丧失。然而，最高剂量的FAUC 329（1 mg/kg）显示出增加MPTP诱导的纹状体DA减少的非显著趋势。FAUC 329对MPTP诱导的DA耗竭的保护作用在延髓核中最为明显，并且似乎与该区域中D3受体的优先丰度有关。靶向中脑边缘DA系统可能对改善受损的运动行为，特别是与延髓核相关的非运动功能具有意义。
We previously synthesised a novel dopamine (DA) partial agonist FAUC 329 with high affinity and selectivity for the DA D3receptor. This is the first in vivo study to investigate the protective effects of FAUC 329 in a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease. Adult male C57bl/6 mice were injected with FAUC 329 (0, 0.1, 0.5, 0.75, or 1mg/kg) 30min before MPTP (2×30mg/kg, 4hr apart). One week later, accumbal and striatal tissue was processed for DA and metabolite HPLC determination as well as immunohistochemical analysis of DA transporter positive neurons in the substantia nigra pars compacta and ventral tegmental area was carried out. FAUC 329 showed a significant attenuation of MPTP-induced DA reduction in the nucleus accumbens (0.5, 0.75 and 1mg/kg) in a dose-dependent manner. FAUC 329 (0.75mg/kg) partly protected against DA depletion in the dorsal striatum as well as protected against loss of DA transporter immunoreactivity in the substantia nigra pars compacta. The highest dose of FAUC 329 (1mg/kg), however, showed a non-significant tendency to augment the MPTP-induced striatal DA reduction. The protective effect of FAUC 329 against MPTP-induced DA depletion was most pronounced in the nucleus accumbens and appears to be linked to the preferential abundance of D3receptors in this region. Targeting the mesolimbic DA system may have implications for improvement of impaired motor behaviour and particularly non-motor functions related to the nucleus accumbens.
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普通狨猴基底神经节中的多巴胺 D3 受体以及 MPTP 和 l-DOPA 治疗后的情况
影响因子：
2.9
作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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作者：
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Sokoloff, P