Efeito de uma sessão de hipóxia intermitente e sua associação com fluoxetina sobre comportamento e parâmetros bioquímicos em camundongos submetidos ao modelo de contenção aguda

Abstract

Mental illnesses are devastating illnesses that affect millions of people around the world. Depression and anxiety have significant financial and emotional costs for patients, families and society. Among the possible causes of these disorders are psychosocial stressors. Thus, exposure to acute restraint stress (ARS) represents an animal model for the induction of depressive and anxious-like behaviors, thus allowing the study of the pathophysiology of these disorders. In addition to the poor understanding of the neurobiology of these disorders, treatment is also limited, as one third of patients do not respond to treatment with antidepressants. In addition, these drugs have several side effects and can take weeks to take effect. Therefore, the discovery and innovation of new treatments/therapies are very important and necessary. Intermittent Hypoxia (IH) is a non-pharmacological alternative treatment that uses breathing with low oxygen concentration interspersed with normoxia periods. HI improves the body's general resistance, being used for pre-acclimatization to altitudes, in sports and in the treatment of various diseases, including mental disorders. Thus, the aim of this study was to investigate the anxiolytic and antidepressant potential, in addition to effects on serum corticosterone levels, oxidative parameters and inflammation, of an acute session (1 hour, 13% O2) of IH and its association with fluoxetine (FLX), in C57BL/6 mice submitted to the ARS model for 6 hours. The open field test (OFT), elevated plus maze test (EPMT), tail suspension test (TST) and forced swimming test (FST) were used to assess anxiety/depressive-like behaviors, which revealed anxiety-like behavior. Regarding oxidative stress, there was a decrease in hydrogen peroxide (H2O2) levels with the associated treatments compared to the control group and greater catalase (CAT) activity in the FLX treatment compared to IH, in the hippocampal tissue. Interleukin IL-17, IL-6 and IFN-γ levels increased after the ARS protocol. All treatments reversed the levels of IFN-γ, IL-17, IL-2 and TNF-α. IL-6 levels were altered by IH+FLX treatment. The results presented in this work demonstrate that ARS was insufficient to induce depressive-like behavior and that only 1 hour of IH and/or its association with fluoxetine did not reverse anxiety-like behavior, but induced changes in oxidative parameters and had an anti-inflammatory effect.