Na+,K+-ATPase activity is increased in rats subjected to chronic administration of ketamine

De Luca RD, Fraga DB, Ghedim FV, Kolling J, Ferreira AGK, Cunha AA, Wyse ATS, Zugno AI. Na+,K+-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.

[1]  L. Crepaldi,et al.  Altered levels of glutamatergic receptors and Na+/K+ ATPase-α1 in the prefrontal cortex of subjects with schizophrenia , 2011, Schizophrenia Research.

[2]  J. Quevedo,et al.  Behavioral changes and mitochondrial dysfunction in a rat model of schizophrenia induced by ketamine , 2011, Metabolic Brain Disease.

[3]  F. Mora,et al.  Prefrontal stimulation of GABAA receptors counteracts the corticolimbic hyperactivity produced by NMDA antagonists in the prefrontal cortex of the rat , 2011, Psychopharmacology.

[4]  J. Quevedo,et al.  A Rodent Model of Schizophrenia Reveals Increase in Creatine Kinase Activity with Associated Behavior Changes , 2010, Oxidative medicine and cellular longevity.

[5]  J. Quevedo,et al.  Na+,K+-ATPase activity in an animal model of mania , 2009, Journal of Neural Transmission.

[6]  G. Agam,et al.  Mitochondrial Complex I Subunits are Altered in Rats with Neonatal Ventral Hippocampal Damage but not in Rats Exposed to Oxygen Restriction at Neonatal Age , 2009, Journal of Molecular Neuroscience.

[7]  C. Shields,et al.  Schizophrenia: a review. , 2007, American family physician.

[8]  A. Aperia.  New roles for an old enzyme: Na,K‐ATPase emerges as an interesting drug target , 2007, Journal of internal medicine.

[9]  Mark Jeremy Hunt,et al.  Ketamine Dose-Dependently Induces High-Frequency Oscillations in the Nucleus Accumbens in Freely Moving Rats , 2006, Biological Psychiatry.

[10]  D. S. Fokkema,et al.  Dose–response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity , 2006, Brain Research Bulletin.

[11]  Nicholas Jones,et al.  Mapping the central effects of ketamine in the rat using pharmacological MRI , 2006, Psychopharmacology.

[12]  V. Balcar,et al.  Glutamatergic hypothesis of schizophrenia: involvement of Na+/K+-dependent glutamate transport. , 2005, Journal of biomedical science.

[13]  A. Grace,et al.  Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia , 2005, Journal of Neural Transmission / General Section JNT.

[14]  P. Ljubuncic,et al.  Dopamine toxicity involves mitochondrial complex I inhibition: implications to dopamine-related neuropsychiatric disorders. , 2004, Biochemical pharmacology.

[15]  C. Netto,et al.  Preconditioning Prevents the Inhibition of Na+,K+-ATPase Activity after Brain Ischemia , 2000, Neurochemical Research.

[16]  F. Mora,et al.  Glutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat , 2004, Journal of Neural Transmission.

[17]  P. A. Kurup,et al.  SCHIZOID NEUROCHEMICAL PATHOLOGY-INDUCED MEMBRANE NA+-K+ ATPASE INHIBITION IN RELATION TO NEUROLOGICAL DISORDERS , 2003, The International journal of neuroscience.

[18]  H. Sauer,et al.  Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a 31P chemical shift spectroscopic-imaging study , 2000, Biological Psychiatry.

[19]  P. Greengard,et al.  A Dopamine/D1 Receptor/Protein Kinase A/Dopamine- and cAMP-Regulated Phosphoprotein (Mr 32 kDa)/Protein Phosphatase-1 Pathway Regulates Dephosphorylation of the NMDA Receptor , 1998, The Journal of Neuroscience.

[20]  M. Smith,et al.  CI-ATPase and Na+/K(+)-ATPase activities in Alzheimer's disease brains. , 1998, Neuroscience letters.

[21]  R. Felder,et al.  Dopamine D2L receptors stimulate Na+/K(+)-ATPase activity in murine LTK- cells. , 1996, Molecular pharmacology.

[22]  B. Moghaddam,et al.  NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  J. McDonald,et al.  Effect of W7 on Ca2+ uptake and Ca2+-ATPase activities of the endoplasmic reticulum of rat liver. , 1987, Archives of biochemistry and biophysics.