A Rodent Model of Schizophrenia Reveals Increase in Creatine Kinase Activity with Associated Behavior Changes

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.

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

“…Standing out amongst the pharmacological animal models of SZ are those which use the administration of non-competitive antagonists of glutamate receptors N-methyl d-aspartate (NMDA), such as ketamine (Ket) (Canever et al 2010, De Oliveira et al 2011. These are responsible for pore blockage within the NMDA channel, which prevents the influx of calcium and can induce a transient and reversible psychotic state, including the positive, negative and cognitive symptoms of SZ in healthy subjects (Mecheri et al 2001).…”

Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia

“…A widely used animal model of schizophrenia involves the acute or repeated administration of ketamine (Becker and Grecksch 2004, Bubeníková-Valesová et al 2008, Canever et al 2010, De Oliveira et al 2011.…”

Zebrafish as a New Platform Used in Exploration of Ketamine-Induced Neurodevelopmental Toxicity

“…The novel tank test [44] indicated that ketamine exposure can reduce anxiety of larval zebrafish in strange environment, which resembles similar results in mice [61,62]. The shoaling test [45] was designed to examine how ketamine exposure altered social behavior of zebrafish shoals.…”

“…And it has been shown that acetyl Lcarnitine's can provide protection against ketamine-induced decrease in heart rate and ERK/MAPK activity though calcium-modulated signaling [61,62]. Further studies are needed to elucidate the mechanism about how acetyl L-carnitine counteracts ketamine's adverse effects on neurons.…”