Efeito do carvacrol na reversão de alterações comportamentais e neuroquímicas induzidas pelo estresse crônico imprevisível

Abstract

Depression is a disabling and recurrent mood disorder in clinical practice. Its etiology is considered multifactorial, as it involves genetic and environmental factors, among which, stress is one of the most studied. Although several classes of antidepressants are available, resistance to treatment still reaches high rates. In this context, compounds from plants offer great potential for the development of new drugs, often safer and more innovative. Carvacrol (Carv) is a monoterpene found in the essential oils of several aromatic plants, such as oregano and thyme, which showed antidepressant and anxiolytic activity in acute stress behavioral models. The present study aimed to investigate the activity of Carv in an animal model of Chronic Unpredictable Stress (CUS). For this, male Swiss mice, 20-24g, were submitted to a 28-day experimental protocol, in which the animals (n = 6-8/group), except the control group, were submitted to environmental stressors, at random. From the 15th day, the experimental groups received, orally: vehicle (saline + 2% Tween 80®), Carv (50 mg/kg) or Fluoxetine (10 mg/kg), as a standard antidepressant. The mice were exposed to the following behavioral tests: Forced Swimming (FS), Open Field (OF), Sucrose Preference (SP), Object Recognition (OR), Social Interaction (SI) and Y Maze (YM). After the behavioral evaluation, the animals were euthanized and the brain areas (prefrontal cortex, striatum and hippocampus) were dissected for the neurochemical evaluation: oxidative stress parameters (MDA, nitrite and GSH) and cytokine dosage (IL-1β and TNFα). Animals submitted to the ECI model developed depressive behavior and cognitive deficit. Carv showed antidepressant activity with decreased immobility time in the FS test, anti-anhedonic in the SP test, and improved social preference in the SI test, being devoid of any effect on locomotor activity, as shown in the OF. In addition, Carv reversed the cognitive deficit caused by ECI in YM and OR. Carv was also able to reverse oxidative damage, decreasing the levels of nitrite and MDA in the three brain areas evaluated, in addition to reversing the decrease in GSH. The ECI model increased the levels of the inflammatory cytokines evaluated (IL-1β and TNFα), which were reduced by the administration of Carv. These results reinforce the hypothesis that Carv presents an antidepressant activity-like related to antioxidant and antiinflamatory effects and may be a pharmacological alternative for the treatment of mood disorders.