Efeito do extrato de frutos de mirtilo e/ou do lítio sobre o status redox e na atividade das enzimas acetilcolinesterase e Na+,K+-ATPase em cérebro de ratos submetidos a um modelo experimental de mania

Abstract

Bipolar disorder is a severe psychiatric disease characterized by recurrent episodes of mania and depression. Considering that this pathology has a negative impact on the life of the patients, the search for neuroprotective agents becomes crucial. The objective of this study was to investigate the protective effects of blueberry fruit extract and/or lithium on oxidative stress parameters, as well as on the activity of the enzymes acetylcholinesterase (AChE) and Na+,K+-ATPase in rat brain submitted to the experimental model of mania induced by ketamine. Male Wistar rats were pretreated with vehicle, blueberry extract (200 mg/kg) and/or lithium (45 mg/kg or 22.5 mg/kg twice daily) for 14 days. Between days 8 and 14, the animals also received an intraperitoneal injection of ketamine (25 mg/kg) or vehicle. On the 15th day the animals received a single injection of ketamine and after 30 minutes the locomotor activity was evaluated through the open field test. The administration of ketamine induced an increase in the locomotor activity of the animals, as well as alterations in oxidative stress parameters, such as increase in the levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and nitrite, besides the decrease in activity of antioxidant enzymes. Pretreatment with blueberry or lithium extract was able to prevent hyperlocomotion as well as the parameters of oxidative stress induced by ketamine in cerebral cortex, hippocampus and striatum. When the blueberry extract was associated with lithium, the alterations were partially prevented. Ketamine increased the activity of the enzymes AChE and Na+,K+- ATPase, while the blueberry extract partially prevented these alterations. Our study demonstrated that the extract of blueberry has neuroprotective capacity against the experimental model of mania, however, more studies should be done to evaluate its effects as an adjuvant.