Estudo dos efeitos comportamentais e do estresse oxidativo do cloridrato de metilfenidato em modelo de depressão induzido por estresse crônico imprevisível em camundongos

Abstract

Low doses administered for short periods of methylphenidate (MPD) have a safe profile and cause positive responses to the brain, being able to treat an acute crisis and knowing that an acute depressive crisis leads to suicidal thoughts, would this treatment be able to avoid a possible suicidal outcome? The pharmacotherapy of Major Depressive Disorder (MDD) is currently based on the monoaminergic hypothesis, however, despite being effective in MDD, many patients demonstrate resistance to the treatment. Given this condition, the dopaminergic system also became a therapeutic target, such as the use of norepinephrine and dopamine reuptake inhibitors, such as MPD, a psychostimulant drug that appears as a possible treatment for MDD. Therefore, the discovery or redirection of drugs aimed at a rapid antidepressant action, with fewer side effects and efficacy in a greater number of patients is desired. Thus, this study aims to verify the behavioral and neurochemical effects of MPD in a model of depression induced by chronic unpredictable stress (CUS) in mice. Adult male Swiss mice were randomly divided into 2 groups and 12 subgroups. In one group, the animals were exposed to stressors for 21 days, and from the 17th day to the 21st day they were administered MPD, fluoxetine or saline solution. In the other group, the one with acute exposure to MPD, the animals were submitted to CUS for 21 days, but only on the last day they received MPD. On the 21st day, 30 minutes after the administration of MPD or SS, the animals were submitted to the following behavioral tests: open field, social interaction, Y-maze and tail suspension tests. Immediately after the behavioral tests, the animals were sacrificed by decapitation and the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were removed to perform the oxidative tests. The MFD was able to reverse the depressive phenotype induced by the chronic unpredictable stress model through acute administration and repeated doses, as well as the increase in oxidative stress in the 3 evaluated parameters, GSH, TBARS and Nitrite, in the 3 studied areas, HC, PFC and ST, when administered for 5 days at doses lower than 2 mg/kg and 5 mg/kg. The rapid effect at lower doses and in five days was positive in both behavioral tests and oxidative tests, yet the effect of acute administration of MPD at lower doses was also able to reverse the negative effects of CUS in behavioral tests, showing that results answered the study's problem question, the MPD can be a strong drug candidate to act against the suicidal act of the individual with a depressive crisis. MPD seems to have a neuroprotective effect at low doses in a short period of administration, perhaps due to an antioxidant effect, thus suggesting a deeper study of this result.