Efeito da riparina II na reversão de alterações comportamentais e neuroquímicas em camundongos submetidos ao modelo de depressão induzida por corticosterona

Abstract

Depression is a common and recurrent disorder, and the leading cause of disability in the world. Studies have suggested the involvement of oxidative stress and neurotrophic factors in the pathogenesis of depression, which has directed the search for new therapeutic agents that present antioxidant and neuroprotective activity. Riparin II (RIP II) is an isolated alkamide of Aniba riparia that presented antidepressant and anxiolytic activity in models of acute stress. This study aimed to investigate the activity of RIP II in an animal model of depression induced by corticosterone (CORT). Female Swiss mice, 22-26g, were used in the experiments and received CORT (20 mg/kg) or vehicle subcutaneously once daily for 22 days. From the 14th day onward, RIP II (50 mg/kg) or Fluvoxamine (50 mg/kg, standard antidepressant) was given orally following CORT injection during the last 8 days of treatment with the hormone. The mice were exposed to the following behavioral tests: forced swimming, tail suspension, open field, sucrose preference, elevated plus maze and Ymaze. After behavioral evaluation, brain areas (pre-frontal cortex, striatum and hippocampus) were dissected for neurochemical evaluation: oxidative stress parameters (MDA, nitrite and GSH) and BDNF dosage. Statistical analysis of the data was performed by one-way ANOVA, followed by Newman-Keuls post-hoc test. The treatment with CORT developed depressive and anxiety-like behavior, and cognitive deficits in the animals. The subchronic administration of RIP II, similarly to the standard antidepressant, showed antidepressant activity decreasing the immobility time in the forced swimming and tail suspension tests, being devoid of effect on the locomotor activity of the animals, as demonstrated in the open field. In addition, RIP II showed anxiolytic activity in the elevated plus maze and reversed the cognitive deficit caused by CORT in the Ymaze. RIP II was also able to reverse the oxidative damage caused by CORT, decreasing levels of nitrite and MDA in the three areas evaluated, in addition to reversing the decrease of GSH in the prefrontal cortex. BDNF levels, which were decreased with CORT administration, were increased with RIP II administration. These results show the antidepressive and neuroprotective effect of RIP II against the stress damages, suggesting that it can later be used as a pharmacotherapeutic alternative in the treatment of depression.