Efeito da quetiapina e antidepressivos clássicos sobre comportamentos tipo depressivos, balanço oxidativo e inflamação em soro de ratos submetidos a estresse crônico na vida adulta

Abstract

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals are resistant to the classic treatments available. Globally, MDD affects millions of individuals annually, generating a high degree of mortality and disability. It is known that chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, studies show that inflammatory changes and oxidative balance are associated with the pathophysiology of depression. Oxidative stress appears to precede an increase in proinflammatory mediators, which, in turn, increase oxidative stress. Quetiapine, a secondgeneration antipsychotic, has been inducing a better therapeutic response when administered to individuals refractory to classic treatments. This study had two main objectives: To evaluate the effect of moderate chronic stress (CMS) on depressive behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant and antiinflammatory effect of quetiapine. Male Wistar rats 50 days old were used. The animals were submitted to CMS protocols for 40 days. At the end of the CMS protocol, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine (20 mg/kg), imipramine (30 mg/kg), and escitalopram (10 mg/kg). Imipramine and escitalopram were used as positive controls. At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. After the behavioral tests, the animals were euthanized, and serum samples were collected to analyze biological mediators. The oxidative evaluation occurred by quantifying quinoneimine, a molecule expressed when the myeloperoxidase enzyme (MPO) is active. Levels of interleukin 6 (IL-6) were analyzed through an ELISA kit. CMS induced an increase in depressive behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is one of the relevant phenomena involved in the etiology of depression and suggesting that quetiapine induces an antidepressant effect, possibly because it beneficially interferes with oxidative and inflammatory mechanisms.