Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain
Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain
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DOI：
10.1046/j.1471-4159.2000.0751694.x
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发表时间：
2000-10-01
影响因子：
4.7
通讯作者：
Lévesque, D
中科院分区：
文献类型：
--
作者：
Beaudry, G;Langlois, MC;Lévesque, D
本研究旨在探讨转录因子核受体家族成员在抗精神病药物治疗精神分裂症中的作用。我们已经确定，使用RT-PCR筛选，神经生长因子诱导B（NGFI-B）的mRNA水平的一个重要的调制典型和非典型的神经阻滞剂，NGFI-B，核受体家族的成员，可以观察到在多巴胺能通路的靶结构。使用原位杂交，我们还表明，典型和非典型抗精神病药物诱导NGFI-B的表达模式的对比后，急性和慢性管理。用氯氮平或氟哌啶醇急性治疗可诱导前额叶和扣带回皮质以及中脑核壳中NGFI-B mRNA水平升高。然而，氟哌啶醇，而不是氯氮平，显着增加NGFI-B的表达在背外侧纹状体。相反，慢性氯氮平治疗降低大鼠前脑NGFI-B表达低于基础水平，而氟哌啶醇仍然诱导背外侧纹状体NGFI-B mRNA水平高，最后，使用双原位杂交技术，我们表明，急性给药两种精神抑制剂增加NGFI-B表达神经降压素含神经元在延髓核壳，而氟哌啶醇在背外侧纹状体中的作用主要在含脑啡肽的神经元中观察到。这些结果是第一次证明，核受体家族成员的转录因子可能发挥重要作用的抗精神病药物的影响。
This study was designed to investigate the possible involvement of members of the nuclear receptor family of transcription factors in the effects of antipsychotic drugs used in the treatment of schizophrenia. We have identified, using RT-PCR screening, an important modulation of nerve growth factor-inducible B (NGFI-B) mRNA levels by typical and atypical neuroleptics in the rat forebrain, NGFI-B, a member of the nuclear receptor family, can be observed in target structures of dopaminergic pathways. Using in situ hybridization, we also demonstrate that typical and atypical antipsychotics induced contrasting patterns of expression of NGFI-B after both acute and chronic administration. An acute treatment with clozapine or haloperidol induces high NGFI-B mRNA levels in the prefrontal and cingulate cortices and in the nucleus accumbens shell. However, haloperidol, but not clozapine, dramatically increases NGFI-B expression in the dorsolateral striatum. In contrast, chronic treatment with clozapine reduces NGFI-B expression below basal levels in the rat forebrain, whereas haloperidol still induces high NGFI-B mRNA levels in the dorsolateral striatum, Finally, using a double in situ hybridization technique, we show that acute administration of both neuroleptics increases NGFI-B expression in neurotensin-containing neurons in the nucleus accumbens shell, whereas the effects of haloperidol in the dorsolateral striatum are mainly observed in enkephalin-containing neurons. These results are the first demonstration that members of the nuclear receptor family of transcription factors could play an important role in the effects of antipsychotic drugs.