Time course of striatal ΔFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment
Time course of striatal ΔFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment
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DOI：
10.1046/j.1460-9568.2003.02469.x
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发表时间：
2003-02-01
影响因子：
3.4
通讯作者：
Cenci, MA
中科院分区：
文献类型：
--
作者：
Andersson, M;Westin, JE;Cenci, MA
DeltaFosB样蛋白是特别稳定的转录因子，在大脑中积累，以响应慢性扰动。在这项研究中，我们比较了纹状体FosB/DeltaFosB样免疫反应性和前强啡肽mRNA表达的时间过程后，停止慢性可卡因治疗的完整大鼠和慢性左旋多巴治疗单方面6-羟基多巴胺（6-OHDA）损伤的大鼠。在最后一次药物注射后3小时至16天之间处死动物。在这两种治疗模式中，药物诱导的FosB/DeltaFosB免疫反应性在尾壳核中仍然显著升高，即使在检查的最长停药期。伴随的前强啡肽mRNA的上调，DeltaFosB的目标，在6-OHDA损伤/L-DOPA模型中DeltaFosB样免疫反应性的时间过程，但在用可卡因治疗的动物中更短暂。这些结果表明，DeltaFosB样蛋白具有优异的体内稳定性。在多巴胺去神经纹状体，这些蛋白质可能会产生持续的影响，其靶基因的表达后，长期停止左旋多巴药物治疗。
DeltaFosB-like proteins are particularly stable transcription factors that accumulate in the brain in response to chronic perturbations. In this study we have compared the time-course of striatal FosB/DeltaFosB-like immunoreactivity and prodynorphin mRNA expression after discontinuation of chronic cocaine treatment to intact rats and chronic L-DOPA treatment to unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. The animals were killed between 3 h and 16 days after the last drug injection. In both treatment paradigms, the drug-induced FosB/DeltaFosB immunoreactivity remained significantly elevated in the caudate putamen even at the longest withdrawal period examined. The concomitant upregulation of prodynorphin mRNA, a target of DeltaFosB, paralleled the time-course of DeltaFosB-like immunoreactivity in the 6-OHDA-lesion/L-DOPA model, but was more transient in animals treated with cocaine. These results suggest that DeltaFosB-like proteins have exceptional in vivo stability. In the dopamine-denervated striatum, these proteins may exert sustained effects on the expression of their target genes long after discontinuation of L-DOPA pharmacotherapy.