Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(-1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1)) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.

译文

他汀类药物越来越多地用于治疗各种疾病,超出了其降低胆固醇的原始适应症。我们先前报道辛伐他汀增加了大鼠前额叶皮层的多巴胺受体 [Q. Wang,W.L. Ting,H. Yang,P.T. Wong,高剂量辛伐他汀上调了大鼠前额叶皮层的多巴胺D(1) 和D(2) 受体表达: 可能参与内皮型一氧化氮合酶,br.J. Pharmacol. 144 (2005) 933-939] 并在帕金森氏病 (PD) 模型中恢复了其下调 [Q. Wang,P.H. Wang,C. McLachlan,P.T. Wong,辛伐他汀可逆转6-羟基多巴胺诱导的帕金森病大鼠前额叶皮层多巴胺D1和D2受体表达的下调,脑Res. 1045 (2005) 229-233]。在这里,我们探讨辛伐他汀治疗对组织多巴胺含量和再摄取的影响。Sprague-Dawley大鼠给予辛伐他汀 (1和10 mg kg(-1) 天 (-1),p.o.) 4周。取出前额叶皮层和纹状体的脑组织以获取多巴胺含量及其再摄取。使用高效液相色谱-质谱仪 (hplc-ms),发现辛伐他汀 (10 mg kg(-1) 天 (-1)) 在纹状体中110% 增加多巴胺含量,但在前额叶皮层中减少76% 与生理盐水治疗组相比。两个大脑区域的多巴胺 (DA) 再摄取均未改变。这些结果表明,高剂量辛伐他汀的慢性治疗可能会影响前额叶皮层和纹状体的DA组织水平,而不会改变DA的再摄取。这可能对精神病和纹状体多巴胺能疾病具有重要的临床意义。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录