Wirtshafter D, Asin K E
Department of Psychology, M/C 285 and Laboratory of Integrative Neuroscience, The University of Illinois at Chicago, 1007 W. Harrison, Chicago, IL 60607-7137, USA.
Brain Res. 2001 Mar 2;893(1-2):202-14. doi: 10.1016/s0006-8993(00)03315-1.
Treatment of intact rats with the full D(1) dopamine agonist A-77636 induced Fos-like immunoreactivity in the medial and, to a lesser extent, the lateral portions of the striatum. Pretreatment with the muscarinic antagonist scopolamine hydrobromide (1.5-6 mg/kg) potentiated the response to A-77636 and eliminated the mediolateral staining gradient seen after A-77636 alone. Similar effects were not produced by scopolamine methylbromide, which fails to cross the blood-brain barrier, demonstrating that the actions of scopolamine were centrally mediated. The effects of scopolamine were further compared to those of the D(2)-like dopamine agonist quinpirole using a factorial design in which subjects were pretreated with either scopolamine, quinpirole, or a combination of the two drugs before receiving A-77636. Pretreatment with either scopolamine or quinpirole increased staining in the lateral striatum, but the combination of the two drugs was no more effective than was quinpirole alone. Pretreatment with quinpirole, but not scopolamine, resulted in a markedly "patchy" pattern of staining and actually suppressed staining in the region between patches in the medial striatum. These findings demonstrate that there are both differences and similarities between the effects of scopolamine and quinpirole on D(1) agonist-induced Fos expression and suggest that although inhibition of cholinergic neurons may be one of the mechanisms through which the effects of quinpirole are produced, other factors must also contribute.
用完全性D(1)多巴胺激动剂A - 77636处理未受损大鼠,可在纹状体的内侧部分诱导出Fos样免疫反应,外侧部分诱导程度较轻。用毒蕈碱拮抗剂氢溴酸东莨菪碱(1.5 - 6毫克/千克)预处理可增强对A - 77636的反应,并消除单独给予A - 77636后出现的内侧-外侧染色梯度。不能透过血脑屏障的甲基溴东莨菪碱未产生类似效应,这表明东莨菪碱的作用是由中枢介导的。使用析因设计将东莨菪碱的效应与D(2)样多巴胺激动剂喹吡罗的效应作进一步比较,在接受A - 77636之前,对实验对象分别用东莨菪碱、喹吡罗或两种药物的组合进行预处理。单独用东莨菪碱或喹吡罗预处理均可增加外侧纹状体的染色,但两种药物联合使用并不比单独使用喹吡罗更有效。用喹吡罗预处理(而非东莨菪碱)会导致明显的“斑块状”染色模式,实际上还会抑制内侧纹状体斑块之间区域的染色。这些发现表明,东莨菪碱和喹吡罗对D(1)激动剂诱导的Fos表达的影响既有差异又有相似之处,这表明虽然抑制胆碱能神经元可能是喹吡罗产生效应的机制之一,但其他因素也必定起作用。