Yamagata K, Suzuki K, Sugiura H, Kawashima N, Okuyama S
Department of Neuropharmacology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan.
Ann N Y Acad Sci. 2000 Sep;914:22-32. doi: 10.1111/j.1749-6632.2000.tb05180.x.
As immediate-early genes (IEGs) are thought to play a critical role in mediating stimulus-induced neural plasticity, IEG response induced by methamphetamine (METH) has been characterized to define the changes in gene expression that may underlie its long-lasting behavioral effects. Although activation of several transcription factor IEGs has been described, little is known about effector IEGs. Here, we have examined whether METH administration affects expression of an effector IEG arc (activity-regulated, cytoskeleton-associated) that encodes a protein with homology to spectrin. Using in situ hybridization, we observed that METH caused a rapid and transient dose-dependent increase in arc mRNA level in the striatum and cortex that was abolished by pretreatment with the specific dopamine D1 receptor antagonist SCH-23390 but not by an atypical neuroleptic clozapine. METH induced arc mRNA in layers IV and VI of the cortex which dopamine receptor are localized to. These results suggest that D1 receptors are coupled to activation of arc gene, which may be involved in functional or structural alterations underlying neural plasticity triggered by METH.
由于即刻早期基因（IEGs）被认为在介导刺激诱导的神经可塑性中起关键作用，所以对甲基苯丙胺（METH）诱导的IEG反应进行了表征，以确定可能是其持久行为效应基础的基因表达变化。尽管已经描述了几种转录因子IEGs的激活，但对效应器IEGs了解甚少。在这里，我们研究了给予METH是否会影响效应器IEG arc（活性调节的细胞骨架相关蛋白）的表达，该蛋白编码一种与血影蛋白具有同源性的蛋白质。使用原位杂交技术，我们观察到METH导致纹状体和皮质中arc mRNA水平迅速且短暂的剂量依赖性增加，用特异性多巴胺D1受体拮抗剂SCH-23390预处理可消除这种增加，但非典型抗精神病药物氯氮平则不能。METH在多巴胺受体所在的皮质IV层和VI层诱导arc mRNA表达。这些结果表明，D1受体与arc基因的激活相关联，这可能参与了由METH触发的神经可塑性潜在的功能或结构改变。
