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Updated: Jun 13, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Aberrant regulation of endogenous ouabain-like factor in bipolar subjects
Rif S El-Mallakh1, Marcus Stoddard, Saeed A Jortani
1Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. rselma01@louisville.edu
Abstract:
Ill phases of bipolar illness are associated with abnormalities in ion regulation and intracellular ion concentrations. Previously, it has been reported that mania is characterised by lower circulating levels of ion regulating endogenous cardenolides, and that bipolar subjects lack the normal seasonal variation of these factors. Since endogenous cardenolides are elaborated in settings of extensive physical activity, euthymic bipolar and psychiatrically normal control subjects were asked to exercise to exhaustion. Plasma concentrations of endogenous cardenolides were measured at baseline, 60 min, peak exercise and post-recovery. Ouabain-like immunoreactive factor (OLF) was lower at baseline (0.005+/-S.D. 0.01 ng/mL in bipolar vs. 0.072+/-0.06 ng/mL in normal control subjects, P=0.019), lower at 60 min (0.007+/-S.D. 0.02 ng/mL in bipolar vs. 0.075+/-0.06 ng/mL in normal control subjects, P=0.029), and tended to be lower at peak exercise (0.009+/-S.D. 0.02 ng/mL in bipolar vs. 0.131+/-0.21 ng/mL in normal control subjects, P=0.15) in bipolar subjects compared to non-psychiatric controls. Other endogenous cardenolides did not vary significantly. The endogenous cardenolide, OLF, may be aberrantly controlled in bipolar illness.
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