Involvement of Na+, K+-ATPase and Endogenous Digitalis-Like Compounds in Depressive Disorders

Inbal Goldstein, Talia Levy, Dana Galili, Haim Ovadia, Raz Yirmiya, Haim Rosen, David Lichtstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Background: Sodium and potassium-activated adenosine triphosphatase (Na+, K+-ATPase) and endogenous digitalis-like compounds (DLC) in the brain have been implicated in the pathogenesis of mood disorders. This hypothesis was examined by the determination of Na+, K+-ATPase/DLC system in parietal cortex of patients with different mood disorders and two animal models of depression. Methods: Na+, K+-ATPase concentrations in human brain synaptosomal fractions, from patients with mood disorders, schizophrenia, and normal individuals, were determined by 3H-ouabain binding assay. Alpha isoforms were quantified by Western blotting. Brain DLC were measured using sensitive enzyme linked immunosorbant assay (ELISA). The effects of ouabain and ouabain-antibodies on behavior were determined in two animal models of depression. Results: 3H-ouabain binding in bipolar patients was significantly lower than in major depressed and schizophrenic patients. Na+, K+-ATPase α isoforms in synaptosomal fractions were not different among the groups. DLC levels in the parietal cortex of bipolar patients were significantly higher than in normal individuals and depressed patients. Injection of lipopolysaccharide (intraperitoneally) to rats elicited depression-like symptoms, which were significantly attenuated by pre-injection of ouabain-antibodies. Injection of ouabain and ouabain-antibodies (intracerebroventricular) reduced depression-like symptoms in the forced swimming test in rats. Conclusions: The results support the possibility that Na+, K+-ATPase and endogenous DLC participate in the pathogenesis of depressive disorders.

Original languageAmerican English
Pages (from-to)491-499
Number of pages9
JournalBiological Psychiatry
Issue number5
StatePublished - 1 Sep 2006

Bibliographical note

Funding Information:
This study was supported in part by The Wolfson Foundation for Scientific Research, The Hebrew University Jerusalem, Israel.


  • Digitalis-like compounds
  • K-ATPase
  • LPS
  • Na
  • forced swimming
  • manic depression
  • mood disorder
  • ouabain


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