RESUMEN
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 (Cortâ¯+â¯Rip IV) and fluvoxamine (Cortâ¯+â¯Flu). Three groups were administrated subcutaneously (SC) with corticosterone (20â¯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, 1â¯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.
Asunto(s)
Amidas/farmacología , Antidepresivos/farmacología , Ansiedad/inducido químicamente , Benzamidas/farmacología , Corticosterona/farmacología , Depresión/inducido químicamente , Etilaminas/farmacología , Tiramina/análogos & derivados , Tiramina/farmacología , Amidas/administración & dosificación , Amidas/uso terapéutico , Anhedonia/fisiología , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/farmacología , Antidepresivos/administración & dosificación , Antidepresivos/uso terapéutico , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corticosterona/administración & dosificación , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Etilaminas/administración & dosificación , Etilaminas/uso terapéutico , Femenino , Fluvoxamina/administración & dosificación , Fluvoxamina/farmacología , Preferencias Alimentarias/fisiología , Suspensión Trasera , Hipocampo/metabolismo , Ratones , Sacarosa , Tiramina/administración & dosificación , Tiramina/uso terapéuticoRESUMEN
Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant-like action of ripIII. Following intraperitoneal administration of ripIII at doses of 25 and 50 mg/kg, there were decreases in the immobility time in the FST and tail suspension test without accompanying changes in ambulation (data not shown). The pretreatment of mice with sulpiride (50 mg/kg, i.p.), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and p-chlorophenylalanine (PCPA, 100 mg/kg, i.p. for, four consecutive days) significantly prevented the anti-immobility effect of ripIII in the FST. On the other hand, the anti-immobility effect of ripIII (50 mg/kg, v.o.) was not altered by pretreatment of mice with SCH23390 (15 µg/kg, i.p.) Furthermore, ripIII potentiated the sleeping latency and sleeping time of the pentobarbital-induced sleeping time test and also potentiated apomorphine (16 mg/kg, i.p.)-induced hypothermia in mice. In conclusion, the present study provides evidence that the antidepressant-like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1- and α2- receptors), and dopaminergic (dopamine D2 receptors) systems.
Asunto(s)
Antidepresivos/uso terapéutico , Benzamidas/uso terapéutico , Encéfalo/efectos de los fármacos , Depresión/tratamiento farmacológico , Neuronas/efectos de los fármacos , Tiramina/análogos & derivados , Administración Oral , Agonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Agonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Animales , Antidepresivos/administración & dosificación , Conducta Animal/efectos de los fármacos , Benzamidas/administración & dosificación , Encéfalo/metabolismo , Brasil , Depresión/metabolismo , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/uso terapéutico , Etnofarmacología , Frutas/química , Frutas/crecimiento & desarrollo , Guyana , Lauraceae/química , Lauraceae/crecimiento & desarrollo , Masculino , Ratones , Neuronas/metabolismo , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/metabolismo , Agonistas de Receptores de Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/uso terapéutico , Tiramina/administración & dosificación , Tiramina/uso terapéuticoRESUMEN
This work presents behavioral effects of methyl ethers of N-(2,6-dihydroxybenzoyl) tyramine (riparin III) isolated from the unripe fruit of Aniba riparia on the open field, elevated plus maze (EPM), rotarod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Riparin III was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg. The results showed that riparin III with both doses had no effects on spontaneous motor activity in mice or in the rotarod test, but decreased the number of grooming and rearing. At the dose of 50 mg/kg, riparin III increased the number of entries in the open arms of the EPM test as compared with control. Similarly, in the hole-board test, both doses increased the number of head dips. There was a reduction on the sleeping latency with both doses and a prolongation of the pentobarbital-induced sleeping time with the dose of 25 mg/kg. In the tail suspension test, similar to imipramine (30 mg/kg), riparin III at the dose of 50 mg/kg presented a reduction in the immobility time. In the forced swimming test, both doses of riparin III decreased the immobility time. These results showed that riparin III potentiated the barbiturate-induced sleeping time and presented antidepressant- and anxiolytic-like effects.