Estudo do efeito do aripiprazol sobre alterações comportamentais e neuroquímicas provocadas pelo modelo animal de depressão induzida por corticosterona

• Ano de defesa: 2019
• Autor(a) principal: Medeiros, Ingridy da Silva
• Orientador(a): Vasconcelos, Silvânia Maria Mendes
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Depressão; Corticosterona; Aripiprazol
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/44161

Major depression affects millions of people and the limited treatment responsiveness have been leading to a search for new therapeutic strategies (e.g. aripiprazole augmentation to the therapeutic scheme for depression). Meanwhile, this augmentation leads to polypharmacy causing an increased risk to side effects. Bearing in mind the atypical antipsychotic’s mechanism of action, we aimed to study the effects of aripiprazole on neurochemical and behavioral changes promoted by an animal model of depression induced by corticosterone. Female Swiss mice were treated with tween 0.03%, as the vehicle (V) or corticosterone 20 mg/kg (CORT) by subcutaneous pathway for the first 14 days. Also, water (V), desvenlafaxine 20 mg/kg (DVS) or aripiprazole 0.5 or 1 mg/kg (ARI) by the oral pathway from 15th day up to 21st day of the experimental protocol. At the latest day, one hour after the last injection we submitted all animals to open field, rotarod, forced swimming, tail suspension, three-chamber sociability and Y maze test. Afterward, all animals were euthanized, and the hippocampus isolated to measure the Brain-Derived Neurotrophic Factor (BDNF), malondialdehyde (MDA) and glutathione (GSH) levels. All animals submitted to the model did not show alterations on the locomotor or exploratory activity compared to the control group. On the other hand, V+ARI 1 showed fewer crossing number when compared to the V+V group. The mice submitted to the model showed a depressive-like behavior and a decreased sociability. Only DVS administration was able to reverse these changes in the depressed group. Regarding the memory deficits induced by the CORT, neither DVS nor ARI reversed these deficits. Regarding the neurochemical parameters, CORT+V group displayed lower levels of BDNF, higher levels of MDA, and lower levels of GSH. ARI 1 reversed these neurotrophic and oxidative markers. DVS injection decreased MDA levels. Whereas ARI 1 increased MDA levels demonstrating a prooxidative effect in the hippocampus. Neither DVS nor ARI reversed GSH-induced deficits in the CORT group. Taken together, our results suggest a lack of antidepressant-like and prooxidative effects of ARI as monotherapy, despite the neurotrophic effect. Altogether, our findings indicate that ARI as a monotherapy is not an effective strategy for major depression.