Gerfen C R, Engber T M, Mahan L C, Susel Z, Chase T N, Monsma F J, Sibley D R
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892.
Science. 1990 Dec 7;250(4986):1429-32. doi: 10.1126/science.2147780.
The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.
纹状体是大脑基底神经节的主要组成部分，部分受黑质多巴胺能输入的调节。帕金森病患者纹状体多巴胺的丧失会导致严重的运动障碍。由6-羟基多巴胺（6-OHDA）引起黑质纹状体多巴胺通路损伤的大鼠可作为帕金森病的模型，并在纹状体向苍白球和黑质的两个主要输出系统中表现出基因表达的改变。纹状体苍白球神经元在编码D2多巴胺受体和脑啡肽的信使核糖核酸（mRNA）的特异性表达上表现出6-OHDA诱导的升高，随后用D2激动剂喹吡罗连续治疗可使其逆转。相反，纹状体黑质神经元在编码D1多巴胺受体和P物质的mRNA的特异性表达上表现出6-OHDA诱导的降低，随后每日注射D1激动剂SKF-38393可使其逆转。这种治疗还会增加纹状体黑质神经元中强啡肽mRNA的表达。因此，多巴胺对纹状体黑质和纹状体苍白球神经元的不同作用分别由它们对D1和D2多巴胺受体亚型的特异性表达介导。
