Chronic treatment with celecoxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in rat brain.
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) (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.
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 10A Datun Road, Chaoyang District, Beijing 100101, PR China. guojy@psych.ac.cn
Jian-You
JY
Guo
Chang-Yu
CY
Li
Ye-Ping
YP
Ruan
Meng
M
Sun
Xiao-Li
XL
Qi
Bao-Sheng
BS
Zhao
Fei
F
Luo
D000818:Animals; D001921:Brain / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib