Hooper M L, Chiasson B J, Robertson H A
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Canada.
Neuroscience. 1994 Dec;63(4):917-24. doi: 10.1016/0306-4522(94)90559-2.
While many studies have examined the numerous physiological and pharmacological factors which can induce the expression of c-fos and other immediate-early genes, few have examined the physiological/biochemical consequences of altering their expression pattern. Using antisense oligonucleotides to c-fos, we demonstrate that D-amphetamine-induced c-fos expression can be attenuated in specific brain regions in vivo. This unilateral attenuation of c-fos expression in D-amphetamine-stimulated animals results in a directed rotational behavior. We show that animals rotate only when they express a difference in Fos-like immunoreactivity between hemispheres. The attenuation of Fos-like immunoreactivity by the antisense oligonucleotides appears to be dependent on the c-fos messenger RNA site that these antisense oligonucleotides target and the degree of chemical protection of the oligonucleotide against degradation. The attenuation of Fos-like immunoreactivity and the increase in unilaterally directed rotation are both time- and dose-dependent. These results demonstrate that manipulating immediate-early gene expression by the direct infusion of antisense oligonucleotides in specific brain regions can have behavioral consequences.
虽然许多研究已经考察了众多能够诱导c-fos及其他即刻早期基因表达的生理和药理因素，但很少有研究考察改变它们表达模式所产生的生理/生化后果。利用针对c-fos的反义寡核苷酸，我们证明在体内特定脑区，右旋苯丙胺诱导的c-fos表达可被减弱。在右旋苯丙胺刺激的动物中，这种c-fos表达的单侧减弱会导致定向旋转行为。我们表明，动物只有在半球间表达出Fos样免疫反应性差异时才会旋转。反义寡核苷酸对Fos样免疫反应性的减弱似乎取决于这些反义寡核苷酸所靶向的c-fos信使核糖核酸位点以及寡核苷酸对降解的化学保护程度。Fos样免疫反应性的减弱和单侧定向旋转的增加均呈时间和剂量依赖性。这些结果表明，通过在特定脑区直接注入反义寡核苷酸来操纵即刻早期基因表达可产生行为后果。
