Reversal effect of Riparin IV in depression and anxiety caused by corticosterone chronic administration in mice.

Mental disorders have a multifactorial etiology and stress presents as one of the causal factors. In depression, it is suggested that high cortisol concentration contributes directly to the pathology of this disease. Based on that, the study aims to evaluate the potential antidepressant effect of Riparin IV (Rip IV) in mice submitted to chronic stress model by repeated corticosterone administration. Female Swiss mice were selected into four groups: control (Ctrl), corticosterone (Cort), Riparin IV (Cort + Rip IV) and fluvoxamine (Cort + Flu). Three groups were administrated subcutaneously (SC) with corticosterone (20 mg/kg) during twenty-one days, while the control group received only vehicle. After the fourteenth day, groups were administrated tested drugs: Riparin IV, fluvoxamine or distilled water, by gavage, 1 h after subcutaneous injections. After the final treatment, animals were exposed to behavioral models such as forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM) and sucrose preference test (SPT). The hippocampus was also removed for the determination of BDNF levels. Corticosterone treatment altered all parameters in behavioral tests, leading to a depressive- and anxious-like behavior. Riparin IV and fluvoxamine exhibit antidepressant effect in FST, TST and SPT. In EPM and OFT, treatment displayed anxiolytic effect without alteration of locomotor activity. Corticosterone administration decreased BDNF levels and Riparin IV could reestablish them, indicating that its antidepressant effect may be related to ability to ameliorate hippocampal neurogenesis. These findings suggest that Riparin IV improves the depressive and anxious symptoms after chronic stress and could be a new alternative treatment for patients with depression.

Riparin II ameliorates corticosterone-induced depressive-like behavior in mice: Role of antioxidant and neurotrophic mechanisms.

Riparin II (RIP II) is an alkamide isolated from Aniba riparia that has presented antidepressant and anxiolytic effects in acute stress behavioral models. This study aimed to investigate the activity of RIP II in a corticosterone-induced depression mice model. Corticosterone (20 mg/kg, s.c.) was administered once a day for 21 days. RIP II (50 mg/kg, p.o.) or fluvoxamine (FLU, 50 mg/kg, standard antidepressant, p.o.) was administered after corticosterone (CORT) injection, for the last 7 days of CORT treatment. 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 (prefrontal cortex, hippocampus and striatum) were dissected for neurochemical evaluation: oxidative stress parameters (MDA, nitrite and GSH) and BDNF dosage. Repeated CORT administration caused depressive-like behavior in mice as indicated by increased despair effects in forced swimming and tail suspension tests and anhedonia in sucrose preference test. In addition, CORT decreased BDNF levels in the mice hippocampus and induced oxidative load in the brain with significative increase in pro-oxidant markers (lipid peroxidation and nitrite levels) and a decline in anti-oxidant defense system (reduced glutathione levels), indicating a direct effect of stress hormones in the induction of the brain oxidative stress. On the other hand, RIP II treatment reversed CORT-induced depressive-like behavior. Furthermore, this treatment reversed the impairment in BDNF levels and oxidative brain insults caused by CORT. This may demonstrate the mechanisms involved in antidepressant-like effect of RIP II. These findings further support that RIP II may be implicated as pharmacological intervention targeting depression associated with HPA-axis dysregulation.

Involvement of monoaminergic system in the antidepressant-like effect of riparin I from Aniba riparia (Nees) Mez (Lauraceae) in mice.

In past studies conducted by our group, riparin I (rip I) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice, while its analogs rip II and III showed anxiolytic and antidepressant-like actions. This time around, we investigated a possible antidepressant activity of rip I using the forced swimming test (FST) and tail suspension test (TST) as predictive tests for antidepressant activity in rodents. In addition, the involvement of the monoaminergic system in this effect was also assessed. rip I was acutely administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that rip I at both tested doses and administration routes produced a significant decrease in immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1 -adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2 -adrenoceptor antagonist), SCH23390 (15 µg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p-chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis) or ritanserin (4 mg/kg, a serotonin 5-HT2(A)/2(C) receptor antagonist) blocked the anti-immobility effects elicited by rip I (50 mg/kg, p.o.) in the FST. Taken together, results indicate that rip I produces significant antidepressant-like activity in the FST and TST, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic and serotonergic systems.