Related Experiment Video
Updated: Jan 4, 2026
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Intracerebroventricular injection of ouabain causes mania-like behavior in mice through D2 receptor activation
Alexander Lopachev1, Anna Volnova2,3, Anna Evdokimenko4
1Research Center of Neurology, Volokolamskoye shosse 80, 125367, Moscow, Russia. lopachev@neurology.ru.
Abstract:
Intracerebroventricular (ICV) administration of ouabain, an inhibitor of the Na, K-ATPase, is an approach used to study the physiological functions of the Na, K-ATPase and cardiotonic steroids in the central nervous system, known to cause mania-like hyperactivity in rats. We describe a mouse model of ouabain-induced mania-like behavior. ICV administration of 0.5 µl of 50 µM (25 pmol, 14.6 ng) ouabain into each lateral brain ventricle results in increased locomotor activity, stereotypical behavior, and decreased anxiety level an hour at minimum. Fast-scan cyclic voltammetry showed that administration of 50 µM ouabain causes a drastic drop in dopamine uptake rate, confirmed by elevated concentrations of dopamine metabolites detected in the striatum 1 h after administration. Ouabain administration also caused activation of Akt, deactivation of GSK3β and activation of ERK1/2 in the striatum of ouabain-treated mice. All of the abovementioned effects are attenuated by haloperidol (70 µg/kg intraperitoneally). Observed effects were not associated with neurotoxicity, since no dystrophic neuron changes in brain structures were demonstrated by histological analysis. This newly developed mouse model of ouabain-induced mania-like behavior could provide a perspective tool for studying the interactions between the Na,K-ATPase and the dopaminergic system.
Insights
We developed a mouse model for ouabain-induced mania-like behavior. Intracerebroventricular ouabain administration increased hyperactivity and decreased anxiety, impacting the dopaminergic system without neurotoxicity.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Intracerebroventricular (ICV) ouabain administration is used to study Na, K-ATPase functions in the central nervous system.
- Ouabain is known to induce mania-like hyperactivity in rats.
Purpose of the Study:
- To develop and characterize a mouse model of ouabain-induced mania-like behavior.
- To investigate the effects of ouabain on the dopaminergic system and related signaling pathways.
- To assess the potential neurotoxicity of ouabain administration.
Main Methods:
- ICV administration of ouabain in mice.
- Behavioral analysis including locomotor activity, stereotypy, and anxiety levels.
- Fast-scan cyclic voltammetry to measure dopamine uptake.
- Measurement of dopamine metabolites and Western blot analysis for signaling proteins (Akt, GSK3β, ERK1/2).
- Histological analysis for neurotoxicity assessment.
- Pharmacological intervention with haloperidol.
Main Results:
- ICV ouabain administration induced mania-like behaviors: increased locomotor activity, stereotypy, and decreased anxiety.
- Ouabain significantly reduced dopamine uptake rate and increased dopamine metabolites in the striatum.
- Activation of Akt and ERK1/2, and deactivation of GSK3β were observed in the striatum.
- Haloperidol attenuated the ouabain-induced behavioral and biochemical effects.
- No evidence of neurotoxicity was found through histological examination.
Conclusions:
- A novel mouse model for ouabain-induced mania-like behavior was successfully established.
- This model demonstrates the involvement of the Na, K-ATPase and the dopaminergic system in mania-like symptoms.
- The model provides a valuable tool for studying the neurobiological underpinnings of mania and the therapeutic potential of targeting the dopaminergic system.
