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.
Guo
Jian-You
JY
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
Li
Chang-Yu
CY
Ruan
Ye-Ping
YP
Sun
Meng
M
Qi
Xiao-Li
XL
Zhao
Bao-Sheng
BS
Luo
Fei
F
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