Moratalla R, Vickers E A, Robertson H A, Cochran B H, Graybiel A M
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
J Neurosci. 1993 Feb;13(2):423-33. doi: 10.1523/JNEUROSCI.13-02-00423.1993.
In cells in culture, specific stimuli induce selective patterns of immediate-early gene induction. In the present study, we tested for such selectivity of stimulated gene expression by monitoring the expression of fos/jun gene mRNAs in the striatum in rats treated in vivo with the indirect dopamine agonist cocaine. We found by Northern blot and in situ hybridization analysis that cocaine induces the coordinate expression of c-fos and jun B mRNAs in neurons of the rat's striatum. By contrast, another immediate-early gene of the leucine-zipper family, c-jun, was not induced in striatal neurons by cocaine at any time tested from 1 to 24 hr after treatment. With the same probe, we could detect the induction of c-jun mRNA (as well as that of c-fos and jun B mRNAs) in the hippocampus following administration of pentylenetetrazol. The induction of expression of c-fos and jun B was rapid and transient, with peak expression occurring at approximately 1 hr after cocaine administration, and the induction of the two genes was in similar striatal sites. These results establish that differential patterns of expression of fos/jun genes occur in striatal neurons following exposure to cocaine, a potent psychomotor stimulant. We suggest that these tissue-specific patterns of gene expression may contribute to the response specificity of striatal neurons to stimulation by monoamines including dopamine.
在培养的细胞中,特定刺激会诱导即刻早期基因的选择性诱导模式。在本研究中,我们通过监测用间接多巴胺激动剂可卡因进行体内处理的大鼠纹状体中fos/jun基因mRNA的表达,来测试刺激基因表达的这种选择性。我们通过Northern印迹和原位杂交分析发现,可卡因可诱导大鼠纹状体神经元中c-fos和jun B mRNA的协同表达。相比之下,在处理后1至24小时的任何测试时间,可卡因都未在纹状体神经元中诱导亮氨酸拉链家族的另一个即刻早期基因c-jun。使用相同的探针,我们可以检测到给予戊四氮后海马中c-jun mRNA(以及c-fos和jun B mRNA)的诱导。c-fos和jun B表达的诱导迅速且短暂,在给予可卡因后约1小时出现峰值表达,并且这两个基因的诱导发生在相似的纹状体部位。这些结果表明,暴露于强效精神运动兴奋剂可卡因后,fos/jun基因在纹状体神经元中出现差异表达模式。我们认为,这些基因表达的组织特异性模式可能有助于纹状体神经元对包括多巴胺在内的单胺类刺激的反应特异性。