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- W2469835523 abstract "Objectives Bipolar disorder ( BD ) is a complex psychiatric disorder characterized by mania and depression. Alterations in brain Na + , K + ‐ ATP ase and cardiac steroids ( CSs ) have been detected in BD , raising the hypothesis of their involvement in this pathology. The present study investigated the behavioral and biochemical consequences of a reduction in endogenous brain CS activity in animal models of mania. Methods Amphetamine ( AMPH )‐induced hyperactivity in BALB /c and black Swiss mice served as a model of mania. Behavior was evaluated in the open‐field test in naïve mice or in mice treated with anti‐ouabain antibodies. CS levels were determined by enzyme‐linked immunosorbent assay ( ELISA) , using sensitive and specific anti‐ouabain antibodies. Extracellular signal‐regulated kinase (ERK) and protein kinase B (Akt) phosphorylation levels in the frontal cortex were determined by western blot analysis. Results Administration of AMPH to BALB /c and black Swiss mice resulted in a marked increase in locomotor activity, accompanied by a threefold increase in brain CSs . The lowering of brain CSs by the administration of anti‐ouabain antibodies prevented the hyperactivity and the increase in brain CS levels. AMPH caused an increase in phosphorylated ERK (p‐ERK) and phosphorylated Akt (p‐Akt) levels in the frontal cortex, which was significantly reduced by administration of the antibodies. A synthetic ‘functional antagonist’ of CS s, 4‐(3′α‐15′β‐dihydroxy‐5′β‐estran‐17′β‐yl) furan‐2‐methyl alcohol, also resulted in attenuation of AMPH ‐induced hyperactivity. Conclusions These results are in accordance with the notion that malfunctioning of the Na + , K + ‐ ATP ase/ CS system may be involved in the manifestation of mania and identify this system as a potential new target for drug development." @default.
- W2469835523 created "2016-07-22" @default.
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- W2469835523 date "2016-07-09" @default.
- W2469835523 modified "2023-10-04" @default.
- W2469835523 title "Endogenous cardiac steroids in animal models of mania" @default.
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- W2469835523 doi "https://doi.org/10.1111/bdi.12413" @default.
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