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吗氯贝胺与司来吉兰在强迫游泳期间行为效应的比较。

Comparison of behavioral effects of moclobemide and deprenyl during forced swimming.

作者信息

Ferigolo M, Barros H M, Marquardt A R, Tannhauser M

机构信息

Division of Pharmacology, Federal Faculty of Medical Sciences of Porto Alegre, RS, Brazil.

出版信息

Pharmacol Biochem Behav. 1998 Jun;60(2):431-7. doi: 10.1016/s0091-3057(98)00011-2.

Abstract

The present study compared the antiimmobility effects of l-deprenyl (DEP) and moclobemide (MOC) to the classic antidepressant imipramine (IMI), using an ethological approach. To investigate the degree of MAO-B inhibition by DEP and MOC, combination of treatments of ineffective doses of phenylethylamine (PHEA) with DEP or with MOC were administered in three doses before immobility was tested in the forced-swimming paradigm. Tests were videotape recorded for analysis of the frequency and duration of the behaviors during the procedure. There was a significant, dose-dependent decrease in immobility duration and an increase in mobility duration of rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior composing 75% of the mobile behaviors. The intermediate doses of the MAOIs tested, DEP 0.25 mg/kg and MOC 30 mg/kg, decreased immobility and increased mobility. The antiimmobility effect of DEP was due to longer climbing behavior while MOC enhanced swimming duration. No behavioral changes were seen with the administration of the lower and higher doses of the MAOI. Potentiation of the antiimmobility effects was observed when ineffective doses of PHEA and of DEP or MOC were administered in combination. Differences between the MAO inhibitors on the active behaviors were also observed when administered with PHEA; DEP and PHEA significantly increased climbing and MOC and PHEA increased swimming. This preclinical evaluation of selective MAO inhibitors indicates that both MAO-A and MAO-B inhibitors have antidepressant effects. However, to clearly demonstrate that these antiimmobility effects are a consequence of increased brain concentrations of any one of the several monoamines implicated in the mechanism of action of DEP or MOC should be the subject of future studies.

摘要

本研究采用行为学方法,比较了左旋司来吉兰(DEP)和吗氯贝胺(MOC)与经典抗抑郁药丙咪嗪(IMI)的抗不动效应。为研究DEP和MOC对单胺氧化酶-B(MAO-B)的抑制程度,在强迫游泳范式中测试不动行为之前,将无效剂量的苯乙胺(PHEA)与DEP或MOC以三种剂量联合给药。对测试过程进行录像,以分析行为的频率和持续时间。接受IMI治疗的大鼠不动持续时间显著剂量依赖性减少,活动持续时间增加。三环类抗抑郁药同等程度地增强了攀爬和游泳这两种主动行为,攀爬行为占活动行为的75%。所测试的单胺氧化酶抑制剂(MAOIs)的中间剂量,即DEP 0.25mg/kg和MOC 30mg/kg,减少了不动时间,增加了活动时间。DEP的抗不动效应归因于更长的攀爬行为,而MOC则增加了游泳持续时间。给予较低和较高剂量的MAOI未观察到行为变化。当无效剂量的PHEA与DEP或MOC联合给药时,观察到抗不动效应增强。当与PHEA联合给药时,也观察到MAO抑制剂在主动行为上的差异;DEP和PHEA显著增加攀爬行为,MOC和PHEA增加游泳行为。对选择性MAO抑制剂的这项临床前评估表明,MAO-A和MAO-B抑制剂均具有抗抑郁作用。然而,要明确证明这些抗不动效应是DEP或MOC作用机制中涉及的几种单胺中任何一种脑浓度增加的结果,应是未来研究的主题。

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