Investigação do efeito antidepressivo da riparina III : alterações comportamentais, neuroquímicas e avaliação do estresse oxidativo

Abstract

Depression is a disabling and recurrent disease whose treatment is related to modulations in monoaminergic systems in several brain areas. Riparin III (ripIII), isolated from unripe fruit of Aniba riparia, has shown previously antidepressant-like effects. Thus, in order to investigate the antidepressant effect of ripIII, behavioral experiments were performed, as the forced swim (FST), tail suspension (TST), apomorphine-induced hypothermia and open field tests. To assess the involvement of monoaminergic system, animals were pretreated with specific antagonists to 5-HT1A-, 5-HT2A/2C-, and 5-HT3-serotonin (5-HT) receptors, to D1- and D2-dopamine (DA) receptors and to 1- and 2-noradrenaline (NA) receptors in FST. Further, animals pretreated with ripIII and submitted or not to the FST had their brain areas such as hippocampus, striatum and prefrontal cortex removed for detection of monoamine levels or to carry out the experiments of oxidative stress, in which, it was investigated enzymatic activities of catalase and superoxide dismutase, measured the levels of reduced glutathione (GSH) and nitrite/nitrate, and lipid peroxidation degree. RipIII was acutely administered orally at a dose of 50 mg/kg in all tests. The results showed that ripIII presented antidepressant effect on the FST and TST suggesting that this effect is specific, since the animals showed no changes in locomotor activity in open field test. In the evaluation of monoaminergic systems, the results showed that the antagonists sulpiride (D2), prazosin (1), yohimbine (2), NAN-190 (5-HT1A) and ondansentron (5-HT3) reversed the immobility time of ripIII on the FST suggesting the involvement of these receptors, while no change of this effect in the presence of the antagonists SCH23390 (D1) and ritanserin (5-HT2A/2C) was observed, suggesting non-participation of these receptors in the drug effect. RipIII was unable to reverse the hypothermia induced by apomorphine that at the dose used, modulates -adrenergic receptors inducing hypothermia, suggesting that the effect of ripIII is not related to these receptors. RipIII, after FST, in the striatum and prefrontal cortex, increased levels of DA, 5-HT and NA, decreased DOPAC, HVA, 5-HIAA metabolites and decreased metabolic rates, and in the hippocampus, increased 5-HT and NA and 5-HIAA metabolite, but maintained metabolic rates. The prior administration of ripIII before the forced swimming, reversed the increased levels of lipid peroxidation and nitrite-nitrate, reduced the activity of catalase but increased levels of GSH in hippocampus, striatum and prefrontal cortex. These parameters were not altered in animals not exposed to stress. In conclusion, the study suggests a modulating action exerted by ripIII on the functioning of the noradrenergic, dopaminergic and serotonergic levels in the brain, as a mechanism for the antidepressant effect in the FST, as well as the participation of direct or indirect antioxidant properties of this drug through the ability to modify the neuronal response to oxidative stress.