Papel de moduladores da via das quinureninas na reversão de sintomas e alterações neuroquímicas tipo-esquizofrenia induzidos pela administração repetida de cetamina em camundongos

• Ano de defesa: 2015
• Autor(a) principal: Araújo, Tatiane da Silva
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Esquizofrenia; Melatonina; Ketamina; Risperidona
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/13887

Schizophrenia is a serious and disabling mental disorder. The pathophysiology is little known and has limitations in drug therapy. Evidence suggests that alterations in the immune system would be associated with schizophrenia by an imbalance in the metabolism of tryptophan through kynurenine pathway and an increase in the production of kynurenic acid. This study investigated the effect of kynurenines pathway modulators in the reversal of schizophrenia-like behavioral and neurochemical changes induced by ketamine in mice. Adult male mice received saline or ketamine for 14 days, and the 8th to the 14th day, additionally received 1-methyl-d-tryptophan (20 or 40 mg / kg), risperidone (0.25 mg / kg) both intraperitoneally, or melatonin (15mg / kg) orally administered 30 minutes later. Schizophrenia-like symptoms were assessed by pre-pulse inhibition (PPI) and locomotor activity, social preference and Y-maze. Oxidative changes (reduced glutathione (GSH) and lipid peroxidation), nitrite levels, inflammatory alterations (myeloperoxidase) and cytokines levels (IL-6 and IL-4) were measured in the prefrontal cortex, hippocampus and the striatum. The result of behavioral tests showed that ketamine promoted the deficit in sensorimotor filter, increased locomotor activity, social interaction, decreased and prejudice work memory. All of these parameters were prevented and reversed by the administration of 1-methyl-D-triptophan (20 or 40 mg/kg), risperidone (0.25mg/kg) and melatonin (15 mg/kg). Ketamine has also promoted an increase in lipid peroxidation, decrease in GSH levels, increased levels of nitrite, inflammatory changes indicated by myeloperoxidase and alterations in levels of proinflammatory (IL-6) and anti-inflammatory (IL-4) cytokines. Accordingly, 1-methyl-d-tryptophan, melatonin and risperidone were able to reverse those changes, except in IL-4 levels. The results suggest that these drugs act like immunomodulators of tryptophan metabolism in kynurenines pathway.