MacGibbon G A, Lawlor P A, Hughes P, Young D, Dragunow M
Department of Pharmacology, University of Auckland, New Zealand.
Brain Res Mol Brain Res. 1995 Dec 28;34(2):294-302. doi: 10.1016/0169-328x(95)00184-t.
The dopamine receptor antagonist, haloperidol, produced a time-dependent differential induction of inducible transcription factors (ITFs) in rat striatal neurons: Fos, Fos B, Jun B, Jun D, Krox 20, and Krox 24, but not c-Jun, were induced in the caudate putamen and nucleus accumbens with varying time courses. The induction of Fos by haloperidol was stronger in anterior versus posterior regions of the striatum. In contrast, induction of Fos by the muscarinic agonist pilocarpine was stronger in the posterior regions of the striatum suggesting that muscarinic receptors do not play a role in the induction of ITFs in striatal neurons by haloperidol. Although c-Jun was not induced in caudate neurons by haloperidol it was strongly induced in these neurons following prolonged seizure activity. The differential pattern of Jun protein expression suggests that haloperidol induces a specific transcriptional program in basal ganglia neurons. These effects of haloperidol may be involved in producing its extrapyramidal side effects.
多巴胺受体拮抗剂氟哌啶醇在大鼠纹状体神经元中产生了诱导型转录因子（ITFs）的时间依赖性差异诱导：尾状壳核和伏隔核中诱导了Fos、Fos B、Jun B、Jun D、Krox 20和Krox 24，但未诱导c-Jun，且诱导过程具有不同的时间进程。氟哌啶醇对Fos的诱导在纹状体前部比后部更强。相比之下，毒蕈碱激动剂毛果芸香碱对Fos的诱导在纹状体后部更强，这表明毒蕈碱受体在氟哌啶醇诱导纹状体神经元中的ITFs过程中不起作用。虽然氟哌啶醇未在尾状核神经元中诱导c-Jun，但在长时间癫痫活动后这些神经元中c-Jun被强烈诱导。Jun蛋白表达的差异模式表明氟哌啶醇在基底神经节神经元中诱导了特定的转录程序。氟哌啶醇的这些作用可能与产生其锥体外系副作用有关。
