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氯胺酮在小鼠体内产生抗抑郁样作用:可能涉及大麻素系统。

Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.

机构信息

Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran.

出版信息

Biomed Pharmacother. 2019 Apr;112:108717. doi: 10.1016/j.biopha.2019.108717. Epub 2019 Feb 28.

DOI:10.1016/j.biopha.2019.108717
PMID:30970516
Abstract

The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses using the forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) in mice. Our results revealed that intra-peritoneal (i.p.) injection of ketamine (5 and 10 mg/kg), a non-competitive NMDA antagonist, dose-dependently produced antidepressant-like effect in the FST. Moreover, i.p. administration of both CB1 and CB2 receptor drugs: ACPA (1 mg/kg; CB1 receptor agonist), AM251 (1 mg/kg; CB1 receptor antagonist), GP1a (2 mg/kg; CB2 receptor agonist) and AM630 (0.5 mg/kg; CB2 receptor antagonist) exhibited antidepressant action. Interestingly, the concomitant administration of ineffective doses of ketamine and cannabinoid receptor antagonists provoked the antidepressant-like effects as compared to control group. It should be considered, all above mentioned doses of drugs could not change locomotor activity in the OFT. It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.

摘要

这项研究的目的是探讨氯胺酮和大麻素系统在调节抑郁相关反应中的可能相互作用,方法是使用强迫游泳试验(FST)、悬尾试验(TST)和旷场试验(OFT)在小鼠中进行。我们的结果表明,腹腔内(i.p.)注射氯胺酮(5 和 10mg/kg),一种非竞争性 NMDA 拮抗剂,剂量依赖性地产生 FST 中的抗抑郁样作用。此外,腹腔内给予 CB1 和 CB2 受体药物:ACPA(1mg/kg;CB1 受体激动剂)、AM251(1mg/kg;CB1 受体拮抗剂)、GP1a(2mg/kg;CB2 受体激动剂)和 AM630(0.5mg/kg;CB2 受体拮抗剂)表现出抗抑郁作用。有趣的是,与对照组相比,同时给予无效剂量的氯胺酮和大麻素受体拮抗剂会引起抗抑郁样作用。应该考虑到,上述所有药物剂量都不能改变 OFT 中的运动活动。似乎氯胺酮和大麻素系统之间的可能相互作用可能调节抑郁相关行为。

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