Protective effects of selective and non-selective cyclooxygenase inhibitors in an animal model of chronic stress

Abstract

Objective Cyclooxygenase isoenzyme is known to be expressed in different regions of brain, and is mainly used for the treatment of pain and inflammation. Recently, it is proposed that cyclooxygenase isoenzyme may also play a key role in the pathophysiology of various brain-related disorders. The present study was aimed to explore the protective effect of cyclooxygenase inhibitors on stress by using an animal model of chronic stress. Methods The animals were forced to swim individually for a period of 6 min every day for 15 d. Then, the behavior (locomotor activity, anxiety and memory) and biochemical (lipid peroxidation, nitrite level, reduced glutathione, and catalase) alterations were assessed. Results Forced swimming for 15 d caused impaired locomotor activity, anxiety-like behavior and decreased percentage of memory retention, as compared to naïve mice (without chronic fatigue treatment). Biochemical analysis revealed significant increases in lipid peroxidation and nitrite level, while levels of reduced glutathione and catalase activity were both decreased. Chronic treatment with naproxen (14 mg/kg, i.p.), rofecoxib (5 mg/kg, i.p.), meloxicam (5 mg/kg, i.p.), nimesulide (5 mg/kg, i.p.) and valdecoxib (10 mg/kg, i.p.) significantly attenuated these behavioral and biochemical (oxidative damage) alterations in chronic-stressed mice. ConclusionThe cyclooxygenase inhibitors could be used in the management of chronic fatigue-like conditions.

CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice

“…Previous studies have found that the COX-dependent production of PG in the brain plays an important role in various animal models of depression [7,8]; however, it is largely unknown which PG subtypes mediate the behavioral changes in these models. Using well-established depression-related models, we here demonstrated that both the genetic and acute pharmacological inhibition of CRTH2 abolished an increase in depression-related behaviors, such as decreased social interaction in the SIT and increased immobility in the FST.…”

“…COX-2 was also demonstrated to be involved in animal depression models. In the forced-swim test (FST), a behavioral despair paradigm, chronic treatment with selective and non-selective COX-2 inhibitors shows antidepressant-like effect [7]. In a chronic unpredictable stress model, treatment with celecoxib blocks decreased sucrose preference, an indicator of a key symptom of depression [8].…”

Cyclooxygenase-2 inhibition reduces anxiety-like behavior and normalizes enhanced amygdala glutamatergic transmission following chronic oral corticosterone treatment

“…Other reports also indicate that COX-2 inhibition after immobilization stress can improve hypoactivity and memory retention (Kumari et al, 2007), and reduce anxiety in a mirror chamber test (Dhir et al, 2006). Treatment with COX inhibitors can reduce depressive-like behavior after chronic unpredictable stress (Guo et al, 2009) and improve mobility and memory in a model of chronic fatigue (Kumar et al, 2010). Despite these studies, the effects of COX-2 inhibition in long-term models of anxiety-like and depressive-like behaviors is limited, and additional investigation is critical for rigorous preclinical target validation.…”

Chronic administration of parecoxib exerts anxiolytic-like and memory enhancing effects and modulates synaptophysin expression in mice

“…Sleep deprivation produces an increase in anxiety-like behavior and cyclooxygenase-2 expression [ 9 ], while substrate-selective inhibition of cyclooxygenase-2 reduces anxiety-like behavior in mice [ 10 ]. cyclooxygenase-2 inhibitors improve stress-induced anxiety-like behavior in mice [ 11 ]. A clinical study showed that preventative administration of cyclooxygenase-2 inhibitor parecoxib exerts anxiolytic effects in patients undergoing total knee arthroplasty [ 12 ].…”