Drago J, Gerfen C R, Westphal H, Steiner H
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Neuroscience. 1996 Oct;74(3):813-23. doi: 10.1016/0306-4522(96)00145-5.
Psychomotor stimulants such as cocaine alter gene expression in neurons of the striatum. Whereas many of these effects are mediated by D1 dopamine receptors, the involvement of other dopamine receptor subtypes or neurotransmitters is likely. To distinguish between these possibilities, regulation by cocaine of immediate-early genes and genes encoding neuropeptides was analysed in mice that lack functional D1 receptors. Gene expression was examined with in situ hybridization histochemistry. In these animals, cocaine failed to induce the immediate-early genes c-fos and zif 268. In contrast, substance P expression was abnormally increased by this drug. These results demonstrate that some of the effects of cocaine on gene regulation are mediated via D1 receptor-dependent mechanisms, as evidenced by the absence of immediate-early gene induction in D1-deficient mice, whereas others also involve additional, non-D1 receptor mechanisms, as shown for substance P expression.
诸如可卡因之类的精神运动性兴奋剂会改变纹状体神经元中的基因表达。虽然其中许多效应是由D1多巴胺受体介导的，但其他多巴胺受体亚型或神经递质也可能参与其中。为了区分这些可能性，我们在缺乏功能性D1受体的小鼠中分析了可卡因对即早基因和编码神经肽的基因的调控作用。采用原位杂交组织化学技术检测基因表达。在这些动物中，可卡因未能诱导即早基因c-fos和zif 268。相反，该药物使P物质的表达异常增加。这些结果表明，可卡因对基因调控的某些效应是通过D1受体依赖性机制介导的，这在缺乏D1受体的小鼠中未诱导即早基因得到证明，而其他效应还涉及额外的非D1受体机制，如P物质的表达所示。
