Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression

Aye Mu Myint, Harry W.M. Steinbusch, Liam Goeghegan, Dirk Luchtman, Yong Ku Kim, Brian E. Leonard

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

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 1β (IL-1β) 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 α (z = -2.205, p = 0.028) and IL-1β (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.

Original languageEnglish
Pages (from-to)65-71
Number of pages7
JournalNeuroImmunoModulation
Volume14
Issue number2
DOIs
Publication statusPublished - 2007 Sep 1

Fingerprint

Celecoxib
Cyclooxygenase 2 Inhibitors
Depression
Interleukin-1
Interleukin-10
Brain
Locomotion
Prefrontal Cortex
Antidepressive Agents
Hypothalamus
Therapeutics
Tumor Necrosis Factor-alpha
Cytokines

Keywords

  • Behaviour
  • Cyclooxygenase 2
  • Depression
  • Immune changes

ASJC Scopus subject areas

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems

Cite this

Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression. / Myint, Aye Mu; Steinbusch, Harry W.M.; Goeghegan, Liam; Luchtman, Dirk; Kim, Yong Ku; Leonard, Brian E.

In: NeuroImmunoModulation, Vol. 14, No. 2, 01.09.2007, p. 65-71.

Research output: Contribution to journalArticle

Myint, Aye Mu ; Steinbusch, Harry W.M. ; Goeghegan, Liam ; Luchtman, Dirk ; Kim, Yong Ku ; Leonard, Brian E. / Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression. In: NeuroImmunoModulation. 2007 ; Vol. 14, No. 2. pp. 65-71.
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AB - 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 1β (IL-1β) 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 α (z = -2.205, p = 0.028) and IL-1β (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.

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