Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat
Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat
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DOI：
10.1007/s002130000468
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发表时间：
2000-07-01
影响因子：
3.4
通讯作者：
Olsson, T
中科院分区：
文献类型：
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作者：
Bjartmar, L;Johansson, IM;Olsson, T
抗抑郁药物在临床起效前有几周的潜伏期。药物诱导的适应性神经元变化的详细机制尚不清楚。为了阐明候选转录因子的基因表达变化的参与，我们用丁螺环酮、氟西汀、8-OH-DPAT和吗氯贝胺治疗大鼠21天。原位杂交用于研究编码NGFI-A、NGFI-B和糖皮质激素受体、MR和GR的mRNA。所有药物治疗后，尤其是吗氯贝胺治疗后，海马结构和大脑皮层中NGFI-A mRNA表达显著增加（增加77-122%），丁螺环酮除外。所有抗抑郁药均诱导海马CA 1/CA 2亚区MR mRNA表达（27-37%），而吗氯贝胺和8-OH-DPAT显著增加GR基因表达，主要在CA 1区（31-44%）。吗氯贝胺处理后，海马CA 3区（23%）和压后颗粒皮质（38%）NGFI-B mRNA显著降低。抗抑郁药物对特定转录因子有选择性作用。这可能是抗抑郁药治疗后神经元和神经内分泌的适应性变化，包括HPA轴负反馈调节。
There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase), with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There ale selective effects of antidepressant drugs on specific transcription factors. These may be important fur adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.