Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression.
BACKGROUND
The olfactory bulbectomised (OBX) rat model is a chronic model of depression in which behavioural and neuroimmunoendocrine changes are reversed only after chronic antidepressant treatment. The cyclooxygenase 2 (COX-2) inhibitor celecoxib has been shown to improve the depressive symptoms in patients with major depression.


METHODS
The association between blood and brain immunological and behavioural changes in chronic treatment with COX-2 inhibitor was explored in the OBX rats and their sham-operated controls.


RESULTS
The OBX group showed significantly higher locomotor activity than the other groups in the first 5 min in the open field. In the home cage emergence test, the OBX group showed a significantly shorter latency period compared to the sham group (z = -3.192, p = 0.001) but there was no difference between the other three groups. In the hypothalamus, the OBX group had a significantly higher interleukin 1beta (IL-1beta) concentration than the OBX + celecoxib group (z = -1.89, p = 0.05) as well as a significantly higher IL-10 concentration (z = -1.995, p = 0.046). In the prefrontal cortex, the OBX group showed significantly higher concentrations of tumour necrosis factor alpha (z = -2.205, p = 0.028) and IL-1beta (z = -3.361, p = 0.001) than the OBX + celecoxib group, but a significantly lower concentration of IL-10 (p = -3.361, p = 0.001) than the OBX + celecoxib group.


CONCLUSIONS
The results of this study supported the potential therapeutic role of the COX-2 inhibitor celecoxib. It is possible that the behavioural changes following the chronic administration of celecoxib to the OBX rats are associated with an attenuation of the increase in the pro-inflammatory cytokines in the brain.
Myint
Aye Mu
AM
Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands.
Steinbusch
Harry W M
HW
Goeghegan
Liam
L
Luchtman
Dirk
D
Kim
Yong Ku
YK
Leonard
Brian E
BE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D003863:Depression / Q000188:drug therapy* / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009830:Olfactory Bulb / Q000601:surgery; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib