Review of animal models of bipolar disorder that alter ion regulation

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.

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

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.

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.