Efeito da quetiapina sobre comportamentos tipo depressivos e níveis de TNF-α no hipocampo de ratos submetidos a estresse crônico na vida adulta

Abstract

Major depressive disorder (MDD) does not have its etiology fully known. It has high degrees of mortality and morbidity, being a psychiatric disorder that affects millions of people worldwide. Chronic stress is one of the relevant factors underlying TDM, and the hippocampus is one of the limbic regions strongly affected by stress. The hippocampus has direct or indirect connections to brain regions involved with MDD. Scientific evidence suggests that the pathophysiology of MDD is associated with peripheral inflammation and in brain regions involved with the disorder. The tumor necrosis factor-alpha (TNF-α) has been reported as one of the increased pro-inflammatory cytokines in depression. TNF-α is at the top of the cytokine network, as it acts as the first sign of the inflammatory response, inducing the production of other cytokines. Even with advances, the pharmacological therapies most used in depressive disorders have several limitations. Quetiapine, a second-generation antipsychotic, has shown efficacy in treating MDD, among other disorders, and has obtained a positive response in patients refractory to traditional treatments. Therefore, this study aimed to evaluate the effect of moderate chronic stress (ECM) and chronic treatment with quetiapine on depressive behaviors and the levels of TNF-α in the hippocampus of adult rats. Male Wistar rats 50 days old were used. These animals were submitted to a stress protocol for 40 days. At the end of the stress protocol, the animals were treated for 14 days with quetiapine (20 mg/kg), imipramine (30 mg/kg) and escitalopram (10 mg/kg) as positive controls. At the end of the treatments, the animals were subjected to behavioral tests in depression and anhedonia models. After the last behavioral test, the animals were euthanized, the brain was dissected, and the hippocampus was removed and stored. The analysis of the TNF-α cytokine in the hippocampus was performed by the ELISA method. ECM induced depressive and anhedonic behavior in animals. Quetiapine reversed these behaviors. ECM promoted an increase in the levels of TNF-α in the hippocampus, and quetiapine decreased. However, the results on TNF-α did not reach statistical significance. This study corroborates other works in the scientific literature, indicating that quetiapine has a therapeutic effect on MDD. One of the possible mechanisms involved in the therapeutic effect of quetiapine is the reduction of inflammatory mediators in brain regions involved with depression.