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.
Highlights
Schizophrenia is a severe psychiatric disorder, it carries a lifetime risk of around 0.5–1% and its early onset and tendency to chronicity mean that its prevalence is relatively high
Disturbs found in brain energy metabolism are important factors that contribute to neuronal damage in patients with schizophrenia.[10,11,12,13,14,15]
Creatine kinase (CK) is an important enzyme that participates of an important system that maintains the energy homeostasis, this regulation of cell homeostasis is done by isoforms mitochondrial and cytosolic and any alteration in the circuit of creatine-phosphocreatine can be an important step for the neurodegenerative process that leads to the loss neuronal in the brain.[16,17]
Summary
Schizophrenia is a severe psychiatric disorder, it carries a lifetime risk of around 0.5–1% and its early onset and tendency to chronicity mean that its prevalence is relatively high. In order to understand the pathologic mechanisms found in this disease, animal models have been used These models are animals prepared that attempt to mimic a human condition of the psychopathology associated with the group of schizophrenia disorders.[4] Many models have already been described including behavioral models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition.[5,6,7,8] An animal model using ketamine is widely accepted; it is a dissociative anesthetic, affecting glutamatergic activity via blockade of the N-methil-D-aspartate (NMDA) receptor.[9] It is already known that ketamine causes individual psychoses in remitted schizophrenic patients and the use of this substance is used to assess positive and negative symptoms of schizophrenia in healthy volunteers.[8] These authors reported that sub-chronically ketamine-treated animals give evidence that ketamine is a useful animal model of schizophrenia. Geyer et al.[4] described in their review that in rats and monkeys, noncompetitive NMDA antagonists, including PCP and ketamine, produce a range of behavioral abnormalities that have important relationships to schizophrenic symptomatology
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