No abstract

Schizophrenia is a debilitating mental disorder characterized by positive (delusions, hallucinations, disorganized speech) and negative (affective flattering, avolition and social withdrawal) symptoms as well as cognitive deficits. The frequency, severity and topography characterize the disorder as heterogeneous, the pathophysiology of schizophrenia is poorly understood. Sub-anesthetic doses of ketamine produce hyperactivity, stereotypy and abnormal social interaction and it is used as a model of schizophrenia. In this study, we induced an animal model by acute sub-anesthetic doses of ketamine and tested different behavioral parameters. We also evaluated the activity of creatine kinase (CK) in brain of rats treated with ketamine. Our results demonstrated that administration of 10, 25 and 50 mg/kg of ketamine induced an increase of covered distance in habituated and non-habituated rats to the behavioral apparatus. Ketamine administration induced significant social deficits and stereotypic behavioral in all doses tested. Finally we evaluated the effect of different doses of ketamine on creatinine kinase (CK) activity and we observed that CK activity is increased inspecific regions of the brain. Our study suggests that our animal model may be used as a model of schizophrenia and that cerebral energy metabolism might be altered in the brain of schizophrenic patients, probably leading to alterations that might be involved in the pathogenesis of schizophrenia.

ATPase activity is increased in rats subjected to chronic administration of ketamine.Objective: Schizophrenia is a devastating psychiatric disorder. Symptoms of schizophrenia can be divided into positive, negative and cognitive, and the physiopathology is still been unknown. Na + ,K + -ATPase is a protein in its role as a maintainer of fluid balance in all mammals and alterations in this enzyme could cause brain abnormalities. The aim of our study was to investigate the activity of this enzyme in rats submitted to chronic administration of ketamine. Methods: Adult male Wistar rats were submitted to sub-anaesthetic doses of the 25 mg/kg ketamine by seven consecutive days and the Na + ,K + -ATPase activity was analysed in prefrontal and hippocampus of rats. Results: We observed an increase in Na + ,K + -ATPase activity in prefrontal cortex administration of 25 mg/kg ketamine. However, ketamine has no effect in hippocampus. Conclusion: This evidence indicates that the alteration in Na + ,K + -ATPase may be related with glutamatergic system and consequently could be related to the development of schizophrenia. Significant OutcomesThe pathophysiology of schizophrenia is still poorly understood we observed (a) Na + ,K + -ATPase activity increased in prefrontal cortex after chronic administration of ketamine; (b) no significant change was found in Na + ,K + -ATPase activity in hippocampus; (c) we suggested that chronic administration of 25 mg/kg ketamine provoked imbalance in energetic metabolism by alter the Na + ,K + -ATPase activity in prefrontal cortex. LimitationsThis study presented some limitations, first, few brain areas were assessed; second, advanced techniques would be needed to confirm the imbalance of energetic metabolism provoke by ketamine treatment.

Pneumococcal meningitis is a life-threatening disease characterized by acute purulent infection of the meninges causing neuronal injury, cortical necrosis and hippocampal apoptosis. Cholinergic neurons and their projections are extensively distributed throughout the central nervous system. The aim of this study was to assess acetylcholinesterase activity in the rat brain after pneumococcal meningitis. In the hippocampus, frontal cortex and cerebrospinal fluid, acetylcholinesterase activity was found to be increased at 6, 12, 24, 48 and 96 hr without antibiotic treatment, and at 48 and 96 hr with antibiotic treatment. Our data suggest that acetylcholinesterase activity could be related to neuronal damage induced by pneumococcal meningitis.