Ibuprofen Protection Against Restrained Chronic Stress-induced Depression in Male Rats

Introduction: Stress predisposes organisms to depression and cognitive impairments, and seems to interact with metabolic homeostasis. The inflammatory response and the upregulation of proinflammatory cytokines are some of the consequences related to chronic stress. In this study, we investigated the preventive effect of chronic administration of ibuprofen, as an inhibitor of cyclooxygenases, on the cognitive and behavioral alterations and the weight gain reduction induced by simultaneous chronic restraint stress in rats. Materials and Methods: Male Wistar rats were subjected to chronic restraint stress and injected daily with the variable doses of ibuprofen or vehicle, for 21 consecutive days. Then, all animals were tested with the forced swim test and passive avoidance conditioning. Also, the weight of the animals was recorded before and after the interventions. Ultimately, plasma interleukin 6 (IL-6) levels were measured. Results: Chronic stress increased depressive-like behaviors, impaired learning, and disrupted the normal weight gain. However, the animals that received the highest dose of ibuprofen showed less depressive-like behaviors, a better avoidance memory, and a higher weight gain. However, the level of plasma IL-6 did not differ significantly between the study groups. Conclusion: The administration of ibuprofen prevents the cognitive and behavioral consequences of chronic stress. During the recovery, the plasma levels of IL-6 were not elevated by stress, and the IL-6 levels did not predict the behavioral performance of the stressed animals. The exact mechanisms of the protective effects of ibuprofen against chronic stress need to be further investigated. Highlights Stress causes depression and cognitive impairments. Stress brings about inflammatory and the upregulation of proinflammatory. Ibuprofen as an inhibitor of cyclooxygenases and preventive effect of chronic administration. Plain Language Summary Stress causes depression and cognitive impairments, and seems to interact with metabolic homeostasis. It causes inflammatory response and the upregulation of proinflammatory. The reciprocal link between the immune and central nervous systems plays a key role in stress-induced neuroinflammation and depression. We think ibuprofen prevent the stress-induced behavioral, cognitive, and weight alterations following a chronic restraint stress model in rats. The highest dose of ibuprofen showed less depressive-like behaviors. Forced Swimming Test (FST) to measure depressive-like behaviors was used. Finally, the plasma level of interleukin 6 (IL-6) was measured, because the IL-6 is an indicator of inflammation in depressed patients.