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

他汀类药物已被用于治疗多种疾病,这些症状超出了降低胆固醇的最初指标。我们先前曾报道辛伐他汀会增加大鼠前额叶皮层中的多巴胺受体[Q.王伟丁宏阳黄,辛伐他汀大剂量上调大鼠前额叶皮层中的多巴胺D(1)和D(2)受体表达:可能与内皮一氧化氮合酶Br有关。 J.Pharmacol。 144(2005)933-939],并在帕金森氏病(PD)模型中恢复了其下调[Q.王凤华Wang C.McLachlan,P.T. Wong,辛伐他汀逆转了6-羟基多巴胺诱导的帕金森病大鼠Brain Res的前额叶皮层中多巴胺D1和D2受体表达的下调。 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大鼠接受辛伐他汀(1和10 mg kg(-1)day(-1),口服)4周。取出前额叶皮层和纹状体的脑组织中的多巴胺含量并重新摄取。使用高效液相色谱质谱仪(HPLC-MS),发现辛伐他汀(10 mg kg(-1)day(-1))在纹状体中可使多巴胺含量增加110%,但在前额叶中减少76%皮层与生理盐水处理组相比。在两个大脑区域中,多巴胺(DA)的再摄取均未改变。这些结果表明,高剂量辛伐他汀的长期治疗可能会影响额叶前额叶皮层和纹状体中的DA组织水平,而不会改变DA的再摄取。这在精神病和纹状体多巴胺能障碍中可能具有重要的临床意义。

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