Differential patterns of induction of NGFI-B, Nor1 and c-fos mRNAs in striatal subregions by haloperidol and clozapine
Differential patterns of induction of NGFI-B, Nor1 and c-fos mRNAs in striatal subregions by haloperidol and clozapine
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DOI：
10.1016/s0006-8993(00)02109-0
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发表时间：
2000-04-28
期刊：
影响因子：
2.9
通讯作者：
Brené, S
中科院分区：
文献类型：
--
作者：
Werme, M;Ringholm, A;Brené, S
最近，类维生素A激活转录机制的紊乱被认为是精神分裂症的危险因素。在这项研究中，我们比较了核孤儿受体 NGFI-B 的 mRNA 调节，在氟哌啶醇和氯氮平急性和慢性治疗后，NGFI-B 与视黄醇 x 受体和相关孤儿核受体 Nor1 与 c-fos mRNA 形成功能性异二聚体。抗精神病药物氟哌啶醇和氯氮平具有不同的临床特征。氟哌啶醇是一种典型的精神安定药，会产生锥体外系副作用 (EPS)，而非典型化合物氯氮平则不会。急性氟哌啶醇治疗增加了伏隔核壳和核以及内侧和外侧尾壳核中的 NGFI-B、Nor1 和 c-fos mRNA。相比之下，氯氮平仅导致伏隔壳中 NGFI-B、Nor1 和 c-fos 的增加。在扣带皮层、感觉皮层或运动皮层中未检测到氟哌啶醇或氯氮平对这些 mRNA 的影响。长期服用氟哌啶醇会导致伏隔核中 NGFI-B mRNA 增加。严重的是，纹状体和伏隔核中 NGFI-B、Nor1 和 c-fos mRNA 水平的增加可能表明神经激活，这可能可用于筛选不产生 EPS 的药物。此外，在氟哌啶醇急性和长期治疗后，NGFI-B（类维生素A信号传导的重要组成部分）水平升高，表明对类维生素A的敏感性发生改变，这可能是有益的抗精神病作用的重要组成部分。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Disturbances of retinoid activated transcription mechanisms have recently been implicated as risk factors for schizophrenia. In this study we have compared the regulation of mRNAs for the nuclear orphan receptor NGFI-B, which forms a functional heterodimer with the retinoid x receptor and the related orphan nuclear receptor Nor1 with c-fos mRNA after acute and chronic treatments with haloperidol and clozapine. The antipsychotic drugs haloperidol and clozapine have different clinical profiles. Haloperidol is a typical neuroleptic giving extrapyramidal side effects (EPS), whereas the atypical compound clozapine does not. Acute haloperidol treatment increased NGFI-B, Nor1 and c-fos mRNAs in nucleus accumbens shell and core as well as medial and lateral caudate putamen. In contrast, clozapine lead to an increase of NGFI-B, Nor1 and c-fos only in the accumbens shell. No haloperidol or clozapine effect on these mRNAs was detected in cingulate, sensory or motor cortex. Chronic haloperidol lead to an increase of NGFI-B mRNA in the accumbens core. Acutely, it is possible that the increased levels of NGFI-B, Nor1 and c-fos mRNA levels in striatum and accumbens might indicate a neural activation which possibly can be used when screening for drugs that do not produce EPS. Also, the increased levels of NGFI-B, which is an important component in retinoid signaling, both after acute and chronic treatments of haloperidol suggests altered sensitivity to retinoids which could be an important component for the beneficial antipsychotic effect. (C) 2000 Elsevier Science B.V. All rights reserved.