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急性哈林碱给药可诱导大鼠海马产生抗抑郁样效应并增加 BDNF 水平。

Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus.

机构信息

Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1425-30. doi: 10.1016/j.pnpbp.2009.07.021. Epub 2009 Jul 24.

DOI:10.1016/j.pnpbp.2009.07.021
PMID:19632287
Abstract

Harmine is a beta-carboline alkaloid that inhibits monoamine reuptake systems. Findings point to an antidepressant effect of the compounds that increases the levels of monoamines after monoamine oxidase inhibition. The present study aims to compare the behavioral effects and the BDNF hippocampus levels of acute administration of harmine and imipramine in rats. To this aim, rats were acutely treated with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and animal behavior was assessed in the forced swimming and open-field tests. Afterwards, hippocampal BDNF protein levels were assessed in imipramine- and harmine-treated rats by ELISA-sandwich assay. We observed that harmine at doses of 10 and 15 mg/kg, and imipramine at 20 and 30 mg/kg reduced immobility time, and increased both climbing and swimming time of rats compared to saline group, without affecting locomotor activity. Acute administration of harmine at the higher dose, but not imipramine, increased BDNF protein levels in the rat hippocampus. Finally, these findings further support the hypothesis that harmine could be a new pharmacological target for the treatment of mood disorders.

摘要

哈尔明是一种β-咔啉生物碱,可抑制单胺再摄取系统。研究结果表明,这些化合物具有抗抑郁作用,能在单胺氧化酶抑制后增加单胺类神经递质的水平。本研究旨在比较哈尔明和丙咪嗪在大鼠体内急性给药的行为效应和 BDNF 海马体水平。为此,大鼠急性给予哈尔明(5、10 和 15mg/kg)和丙咪嗪(10、20 和 30mg/kg),并在强迫游泳和旷场试验中评估动物行为。之后,通过 ELISA 夹心测定法评估丙咪嗪和哈尔明处理大鼠的海马体 BDNF 蛋白水平。我们观察到,与生理盐水组相比,10mg/kg 和 15mg/kg 的哈尔明以及 20mg/kg 和 30mg/kg 的丙咪嗪可减少大鼠的不动时间,并增加大鼠的攀爬和游泳时间,而不影响其运动活性。急性给予较高剂量的哈尔明而非丙咪嗪可增加大鼠海马体中的 BDNF 蛋白水平。最后,这些发现进一步支持了哈尔明可能成为治疗情绪障碍的新的药理学靶点的假设。

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