Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments
Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments
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DOI：
10.1016/j.brainres.2008.03.023
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发表时间：
2008-05-23
期刊：
影响因子：
2.9
通讯作者：
Lucki, Irwin
中科院分区：
文献类型：
--
作者：
Balu, Darrick T.;Hoshaw, Brian A.;Lucki, Irwin
抗抑郁治疗已被提出通过提高大脑中的神经营养素水平来产生治疗效果。目前的实验研究了不同药物和躯体抗抑郁药物的急性和慢性治疗对大鼠与抑郁相关的几个脑区BDNF蛋白水平的影响。反复应用电休克(ECS)(10天)，但没有单一治疗(1天)，在海马区、额叶皮质、杏仁核和脑干中BDNF蛋白增加了40%-100%。慢性(21天)，但不急性(1天)，三环类抗抑郁剂(TCA)地昔帕明(10 mg/kg)，选择性5-羟色胺再摄取抑制剂(SSRI)氟西汀(10 mg/kg)和单胺氧化酶抑制剂(MAOI)苯乙肼(10 mg/kg)增加额叶皮质(10-30%)BDNF蛋白水平，但不增加海马区、杏仁核、嗅球和脑干BDNF蛋白水平。为了确定脑源性神经营养因子的调节是否是抗抑郁药物治疗所独有的，还研究了用于治疗精神分裂症和焦虑的药物。慢性给予典型抗精神病药物氟哌啶醇(1 mg/kg)和非典型抗精神病药物氯氮平(20 mg/kg)仅使额叶皮质BDNF水平增加8-10%。氟哌啶醇也提高了杏仁核中BDNF的水平，而氯氮平则降低了嗅球中的BDNF水平。苯二氮卓类药物氯氮卓酮(10 mg/kg)的急性或慢性治疗不会改变脑源性神经营养因子水平。这些结果表明，尽管不同的药物和躯体抗抑郁药物以及抗精神病药物在神经递质系统中具有不同的作用机制，但它们仍能增加额叶皮质中BDNF蛋白的水平。(C)2008爱思唯尔B.V.保留所有权利。
Antidepressant treatments have been proposed to produce their therapeutic effects, in part, through increasing neurotrophin levels in the brain. The current experiments investigated the effects of acute and chronic treatment with different pharmacologic and somatic antidepressant treatments on protein levels of BDNF in several brain regions associated with depression in the rat. Repeated applications (10 days) of electroconvulsive shock (ECS), but not a single treatment (1 day), produced 40-100% increases of BDNF protein in the hippocampus, frontal cortex, amygdala, and brainstem. Chronic (21 days), but not acute (1 day), treatment with the tricyclic antidepressant (TCA) desipramine (10 mg/kg), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10 mg/kg), and the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg) increased BDNF protein levels in the frontal cortex (10-30%), but not in the hippocampus, amygdala, olfactory bulb, and brain stem. To determine whether the regulation of BDNF was unique to antidepressant treatments, drugs used to treat schizophrenia and anxiety were also studied. Chronic administration of the typical antipsychotic haloperidol (1 mg/kg) and the atypical antipsychotic clozapine (20 mg/kg) increased BDNF levels by only 8-10% in the frontal cortex. Haloperidol also elevated BDNF levels in the amygdala, while clozapine decreased BDNF in the olfactory bulb. Acute or chronic treatment with the benzodiazepine chlordiazepoxide (10 mg/kg) did not alter BDNF levels. These results suggest that diverse pharmacologic and somatic antidepressant treatments, as well as antipsychotics, increase levels of BDNF protein in the frontal cortex, even though they have different mechanisms of action at neurotransmitter systems. (C) 2008 Elsevier B.V. All rights reserved.