Effects of escitalopram and ibuprofen on a depression-like phenotype induced by chronic stress in rats

Clinical and preclinical studies have reported that co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and antidepressant drugs are effective in patients with depression and in animal models of depression. However, several studies have suggested that NSAIDs inhibit the antidepressant effects of selective serotonin reuptake inhibitors in humans and mice. The present study investigated the effects of escitalopram (ESC) and ibuprofen (IBU), alone or in combination, on the stress-induced behavior and expression of brain-derived neurotrophic factor (BDNF) and p11, markers of depression and antidepressant action, in chronically stressed rats. Rats were subjected to chronic restraint stress (CRS) for 3 weeks and administered the following drugs: single administration of ESC or IBU or co-administration of ESC and IBU (ESC + IBU). Immobility time was measured by the forced swimming test (FST), and hippocampal BDNF and p11 levels were analyzed by quantitative real-time polymerase chain reaction and Western blotting. CRS increased immobility time on the FST. Administration of ESC, IBU, or ESC + IBU significantly attenuated the stress-induced increase in immobility time. CRS also significantly increased plasma corticosterone concentration by 169%. This effect was significantly recovered by administering ESC, IBU, or ESC + IBU. The levels of BDNF and pll in the hippocampus decreased significantly in response to CRS. These decreases were prevented by administering ESC, IBU, or ESC + IBU. These findings suggest that both single and co-administration of ESC and IBU exerts antidepressant effects. These effects were associated with upregulation of BDNF and p11 expression.