Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec:107:208-214.
doi: 10.1016/j.neubiorev.2019.09.016. Epub 2019 Sep 12.

Review of animal models of bipolar disorder that alter ion regulation

Aaron A Mack  1 , Yonglin Gao  2 , Mariusz Z Ratajczak  3 , Sham Kakar  4 , Rif S El-Mallakh  2
Affiliations
Review

Review of animal models of bipolar disorder that alter ion regulation

Aaron A Mack et al. Neurosci Biobehav Rev. 2019 Dec.

Abstract

Background: Accurate modeling of psychiatric disorders in animals is essential for advancement in our understanding and treatment of the severe mental illnesses. Of the multiple models available for bipolar illness, the ones that disrupt ion flux are currently the only ones that meet the three criteria for validity: face validity, construct validity, and predictive validity.

Methods: A directed review was performed to evaluate animal models for mania in which ion dysregulation was the key intervention.

Results: Three models are identified. All focus on disruption of the sodium potassium pump. One is pharmacologic and requires surgical insertion of an intracerebroventricular (ICV) cannula and subsequent administration of ouabain. Two are genetic and are based on heterozygote knockout (KO) of the alpha2 or alpha3 subunits of the sodium pump. Alpha2 KOs are believed to have altered glial function, and they do not appear to have a full array of manic symptoms. Alpha3 KOs appear to be the best characterized animal model for bipolar disorder currently available.

Conclusion: Animal models that disrupt ion regulation are more inclined to model both mania and depression; and are thus the most promising models available. However, other models are important for demonstrating mechanisms in important pathophysiologic aspect of bipolar disorder.

Keywords: Bipolar Animal models; Genetic models of Bipolar disorder; Ion dysregulation in bipolar models.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

References

    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM–5). Washington, DC: American Psychiatric Press, 2013
    1. Arban R, Maraia G, Brackenborough K, Winyard L, Wilson A, Gerrard P, Large C. Evaluation of the effects of lamotrigine, valproate and carbamazepine in a rodent model of mania. Behav Brain Res. 2005; 158:123–132. - PubMed
    1. Bagrov A, Shapiro J, and Fedorova O. Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets. Pharmacological Reviews 2009; 61(1): 9–38; DOI: 10.1124/pr.108.000711 - DOI - PMC - PubMed
    1. Bano D, Nicotera P. Ca2+ signals and neuronal death in brain ischemia. Stroke 2007; 38(2):674–676 - PubMed
    1. Bennett V, Lambert S. Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels. J Neurocytol. 1999; 28:303–318. - PubMed

Publication types

MeSH terms

Substances