Skip to main content Accessibility help

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

  • Renata D. De Luca (a1), Daiane de B. Fraga (a1), Fernando V. Ghedim (a1), Janaína Kolling (a2), Andrea G. K. Ferreira (a2), Aline A. Cunha (a2), Angela T. S. Wyse (a2) and Alexandra I. Zugno (a1)...


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.


Corresponding author

Professor Alexandra Ioppi Zugno, Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. Tel: +55 48 3431 2792; Fax: +55 48 3431 2759; E-mail:


Hide All
1. Schultz, SH, North, SW, Shields, CG. Schizophrenia: a review. Am Fam Physician 2007;75:18211829.
2. Hunt, MJ, Raynaud, B, Garcia, R. Ketamine dose-dependently unduces high-frequency oscillations in the nucleus accumbens in freely moving rats. Biol Psychiatry 2006;60:12061214.
3. Littlewood, CL, Jones, N, O'neill, MJ. Mapping the central effects of ketamine in the rat using pharmacological MRI. Psychopharmacology 2006;186:6481.
4. Grace, AA. Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia. J Neural Transm 1993;91:111134.
5. Aperia, A. New roles for an old enzyme: Na,K-ATPase emerges as an interesting drug target. J Intern Med 2007;261:4452.
6. Wyse, AT, Streck, EL, Worm, P, Wajner, A, Ritter, F, Netto, CA. Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain ischemia. Neurochem Res 2000;25:971975.
7. Nanitsos, EK, Nguyen, KT, St'astný, F, Balcar, VJ. Glutamatergic hypothesis of schizophrenia: involvement of Na+/K+-dependent glutamate transport. J Biomed Sci 2005;12:9712.
8. Hattori, N, Kitagawa, K, Higashida, T et al. CI-ATPase and Na+/K(+)-ATPase activities in Alzheimer's disease brains. Neurosci Lett 1998;2:5414154144.
9. Zugno, AI, Valvassori, SS, Scherer, EB et al. Na+,K+-ATPase activity in an animal model of mania. J Neural Transm 2009;116:431446.
10. Canever, L, Oliveira, L, De Luca, R et al. A rodent model of schizophrenia reveals increase in creatine kinase activity with associated behavior changes. Oxid Med and Cell Longevity 2010;3:421427.
11. Oliveira, L, Fraga, DB, De Luca, RD et al. Behavioral changes and mitochondrial dysfunction in a rat model of schizophrenia induced by ketamine. Metab Brain Dis 2011;26:6977.
12. Imre, G, Fokkema, DS, Den Boer, JA, Ter Horst, GJ. Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity. Brain Res Bull 2006;69:338346.
13. Chan, KM, Delfert, DM, Koepnick, SL, McDonald, JM. Effect of W7 on Ca2+ uptake and Ca2+-ATPase activities of the endoplasmic reticulum of rat liver. Arch Biochem Biophys 1987;256:472479.
14. Verma, A, Moghaddam, B. NMDA receptor antagonists impair prefrontal cortex function as accessed via spatial delayed alternation performance in rats: modulation by dopamine. J Neurosci 1996;16:373379.
15. Yamaguchi, I, Walk, SF, Jose, PA, Felder, RA. Dopamine D2L receptors stimulate Na+/K(+)-ATPase activity in murine LTK- cells. Mol Pharmacol 1996;49:373378.
16. Snyder, GL, Fienberg, AA, Huganir, RL, Greengard, P. 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. J Neurosci 1998;18:1029710303.
17. Ben-Shachar, D, Zuk, R, Gazawi, H, Ljubuncic, P. Dopamine toxicity involves mitochondrial complex I inhibition: implications to dopamine-related neuropsychiatric disorders. Biochem Pharmacol 2004;67:19651974.
18. Volz, HR, Riehemann, S, Maurer, I et al. Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31) P chemical shift spectroscopic-imaging study. Biol Psychiatry 2000;47:954961.
19. Ben-Shachar, D, Nadri, C, Karry, G, Agam, G. Mitochondrial complex I subunits are altered in rats with neonatal ventral hippocampal damage but not in rats exposed to oxygen restriction at neonatal age. J Mol Neurosci 2009;38:143151.
20. Kurup, Rk, Kurup, PA. Schizoid neurochemical pathology-induced membrane Na(+)-K+ ATPase inhibition in relation to neurological disorders. Int J Neurosci 2003;113:17051717.
21. Del Arco, A, Ronzoni, G, Mora, F. Prefrontal stimulation of GABAA receptors counteracts the corticolimbic hyperactivity produced by NMDA antagonists in the prefrontal cortex of the rat. Psychopharmacology 2011;214:525536.
22. Del Arco, A, Mora, F. Glutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat. J Neural Transm 2005;112:97109.
23. Corti, C, Xuereb, JH, Crepaldi, L, Corsi, M, Michielin, F, Ferraguti, F. Altered levels of glutamatergic receptors and Na+/K+ ATPase α1 in the prefrontal cortex of subjects with schizophrenia. Schizophr Res 2011;128:714.


Related content

Powered by UNSILO

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

  • Renata D. De Luca (a1), Daiane de B. Fraga (a1), Fernando V. Ghedim (a1), Janaína Kolling (a2), Andrea G. K. Ferreira (a2), Aline A. Cunha (a2), Angela T. S. Wyse (a2) and Alexandra I. Zugno (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.