Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain

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	Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain
	Guo, Jian-You1 ; Li, Chang-Yu 2; Ruan, Ye-Ping 2; Sun, Meng 1; Qi, Xiao-Li1 ; Zhao, Bao-Sheng 3; Luo, Fei1 ; J. Y. Guo ; F. Luo
摘要	Recent clinical trails reported that adjunctive cyclooxygenase (COX)-2 inhibition with celecoxib is beneficial in treating depression. However, another clinical study showed celecoxib did not have inhibitory effect of COX-2 in human brain when given at a therapeutic dose. Therefore, whether celecoxib is exerting its influence through COX inhibition or by some other mechanism remains unclear. The present study further investigated the effect of celecoxib on COX-2 expression, prostaglandin E2 (PGE2, a major COX-2-mediated inflammatory mediator) concentration and the depressive-like behaviors in rats. Celecoxib was administrated by oral gavage to naive rats (16 mg/kg) or stressed rats (2, 8, 16 mg/kg, respectively) for 21 days, or to stressed rats for a single dose (16 mg/kg). The results showed that 21 days chronic unpredictable stress induced depressive-like behaviors and increased the COX-2 expression and PGE2 concentration in rat brain. Chronic treatments with celecoxib alleviated the depressive-like behavior and reversed the levels of COX-2 expression and PGE2 concentration in stressed rat in a dose-dependent manner. Celecoxib also improved the emotional state and decreased COX-2 expression and PGE2 concentration in naive rats. In addition, a single dose of celecoxib treatment reversed COX-2 expression and PGE2 concentration, but didn't alter the depressive-like behavior in stressed rat. These results suggest that COX-2 enzyme might play a key role in pathophysiology of depression. Furthermore, these data indicate that chronic celecoxib treatment reverse chronic unpredictable stress-induced depressive-like behavior might via reducing COX-2 enzyme in brain, and the selective COX-2 inhibitors could be developed as potential remedies for the management of depression.; Recent clinical trails reported that adjunctive cyclooxygenase (COX)-2 inhibition with celecoxib is beneficial in treating depression. However, another clinical study showed celecoxib did not have inhibitory effect of COX-2 in human brain when given at a therapeutic dose. Therefore, whether celecoxib is exerting its influence through COX inhibition or by some other mechanism remains unclear. The present study further investigated the effect of celecoxib on COX-2 expression, prostaglandin E(2) (PGE(2), a major COX-2-mediated inflammatory mediator) concentration and the depressive-like behaviors in rats. Celecoxib was administrated by oral gavage to naive rats (16 mg/kg) or stressed rats (2, 8, 16 mg/kg, respectively) for 21 days, or to stressed rats for a single dose (16 mg/kg). The results showed that 21 days chronic unpredictable stress induced depressive-like behaviors and increased the COX-2 expression and PGE(2) concentration in rat brain. Chronic treatments with celecoxib alleviated the depressive-like behavior and reversed the levels of COX-2 expression and PGE2 concentration in stressed rat in a dose-dependent manner. Celecoxib also improved the emotional state and decreased COX-2 expression and PGE(2) concentration in naive rats. In addition, a single dose of celecoxib treatment reversed COX-2 expression and PGE(2) concentration. but didn't alter the depressive-like behavior in stressed rat. These results suggest that COX-2 enzyme might play a key role in pathophysiology of depression. Furthermore, these data indicate that chronic celecoxib treatment reverse chronic unpredictable stress-induced depressive-like behavior might via reducing COX-2 enzyme in brain, and the selective COX-2 inhibitors could be developed as potential remedies for the management of depression. (C) 2009 Elsevier B.V. All rights reserved.
关键词	Celecoxib Depressive-like behavior Chronic unpredictable stress Cyclooxygenase-2 Prostaglandin E2
学科领域	健康心理学 ; 临床与咨询心理学
	2009-06-10
语种	英语
发表期刊	EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN	0014-2999
卷号	612 期号:1-3 页码:54-60
期刊论文类型	Article
收录类别	SCI
WOS记录号	WOS:000267150900009
引用统计	被引频次：123[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/5255
专题	中国科学院心理研究所回溯数据库(1956-2010)
通讯作者	J. Y. Guo; F. Luo
作者单位	1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China 2.Zhejiang Chinese Med Univ, Hangzhou 310053, Peoples R China 3.Beijing Univ Chinese Med, Beijing 100029, Peoples R China
第一作者单位	中国科学院心理健康重点实验室
推荐引用方式 GB/T 7714	Guo, Jian-You,Li, Chang-Yu,Ruan, Ye-Ping,et al. Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2009,612(1-3):54-60.
APA	Guo, Jian-You.,Li, Chang-Yu.,Ruan, Ye-Ping.,Sun, Meng.,Qi, Xiao-Li.,...&F. Luo.(2009).Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain.EUROPEAN JOURNAL OF PHARMACOLOGY,612(1-3),54-60.
MLA	Guo, Jian-You,et al."Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain".EUROPEAN JOURNAL OF PHARMACOLOGY 612.1-3(2009):54-60.

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