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评估N-甲基-D-天冬氨酸受体功能在抗抑郁样活性中的作用。西酞普兰和氟西汀在小鼠强迫游泳试验中的一项新研究。

Evaluation of the role of NMDA receptor function in antidepressant-like activity. A new study with citalopram and fluoxetine in the forced swim test in mice.

作者信息

Wolak Małgorzata, Siwek Agata, Szewczyk Bernadeta, Poleszak Ewa, Bystrowska Beata, Moniczewski Andrzej, Rutkowska Anita, Młyniec Katarzyna, Nowak Gabriel

机构信息

Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

出版信息

Pharmacol Rep. 2015 Jun;67(3):490-3. doi: 10.1016/j.pharep.2014.12.003. Epub 2014 Dec 17.

DOI:10.1016/j.pharep.2014.12.003
PMID:25933959
Abstract

BACKGROUND

The NMDA/glutamate receptors are involved in the mechanism of antidepressant activity.

METHODS

The present study was designed to investigate the effect of NMDA receptor ligands (agonists and antagonists of glutamate sites) on the antidepressant-like activity of selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, in the forced swim test in mice.

RESULTS

The antidepressant activity (reduction in immobility time) of citalopram but not of fluoxetine was antagonized by N-methyl-D-aspartate acid and enhanced by CGP37849 (antagonist of the NMDA receptor).

CONCLUSIONS

The present literature data indicate that the antidepressant-like activity of conventional antidepressants is generally affected by the NMDA receptor, although by modulation from different sites of the complex. Thus, it supports the issue of the ability of NMDA receptor antagonists to enhance the antidepressant action in human depression.

摘要

背景

N-甲基-D-天冬氨酸/谷氨酸受体参与抗抑郁活性机制。

方法

本研究旨在探究N-甲基-D-天冬氨酸受体配体(谷氨酸位点的激动剂和拮抗剂)对选择性5-羟色胺再摄取抑制剂(SSRI)西酞普兰和氟西汀在小鼠强迫游泳试验中抗抑郁样活性的影响。

结果

N-甲基-D-天冬氨酸拮抗了西酞普兰的抗抑郁活性(不动时间减少),但未拮抗氟西汀的抗抑郁活性,而CGP37849(N-甲基-D-天冬氨酸受体拮抗剂)增强了西酞普兰的抗抑郁活性。

结论

目前的文献数据表明,传统抗抑郁药的抗抑郁样活性通常受N-甲基-D-天冬氨酸受体影响,尽管是通过该复合体不同位点的调节。因此,这支持了N-甲基-D-天冬氨酸受体拮抗剂增强人类抑郁症抗抑郁作用的能力这一问题。

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