Bhat R V, Cole A J, Baraban J M
Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
J Psychiatry Neurosci. 1992 Sep;17(3):94-102.
Rapid activation of transcription factor genes is thought to play a key role in stimulus-induced neuronal plasticity. To help understand the genomic response that may underlie long-term effects of cocaine and amphetamine, we have investigated the effect of these agents on Zif268, a transcription regulatory factor that is expressed at high levels in brain neurons. Like c-fos, zif268 is markedly activated in striatum by cocaine and amphetamine. This response appears to involve the dopamine system, since it is abolished by SCH23390, a selective D1 dopamine receptor antagonist, or by 6-hydroxydopamine lesions. To assess the role of other monoamine systems in regulating the expression of these transcription factors, we have examined the effects of selective monoamine uptake blockers as well as agents that lesion the norepinephrine and serotonin systems. These studies indicate that, in addition to the dopamine system, the norepinephrine and serotonin systems also play prominent roles in the activation of zif268 and c-fos by cocaine and amphetamine.
转录因子基因的快速激活被认为在刺激诱导的神经元可塑性中起关键作用。为了帮助理解可能是可卡因和安非他命长期影响基础的基因组反应，我们研究了这些药物对Zif268的影响，Zif268是一种在脑神经元中高水平表达的转录调节因子。与c-fos一样，Zif268在纹状体中被可卡因和安非他命显著激活。这种反应似乎涉及多巴胺系统，因为它被选择性D1多巴胺受体拮抗剂SCH23390或6-羟基多巴胺损伤所消除。为了评估其他单胺系统在调节这些转录因子表达中的作用，我们研究了选择性单胺摄取阻滞剂以及损伤去甲肾上腺素和血清素系统的药物的影响。这些研究表明，除了多巴胺系统外，去甲肾上腺素和血清素系统在可卡因和安非他命对Zif268和c-fos的激活中也起重要作用。
