Different behaviors and different strains: potential new ways to model bipolar disorder.

The state of animal models for bipolar disorder (BPD) is deficient, creating a major problem in the research related to this devastating disorder and in our ability to translate molecular findings to the clinic. An ideal model, a "bipolar animal" is most likely unattainable as long as we do not fully understand the biological basis of the disorder, and no models are currently available to reflect the cycling nature of the disease. Yet, additional, better and more practical models need to be developed to support research efforts in the field. The present paper suggests two approaches for the development of new models. The first approach, recently introduced in the literature, is based on modeling different facets of the disease with an attempt to create a test battery that will cover a number of BPD-related behaviors. Whereas each separate model may not have strong validity when used alone, additional strength may come when certain models are combined. One example for modeling a facet of the disorder is brought showing that aggressive behavior in resident mice can be ameliorated by the dissimilar mood stabilizers lithium and valproate suggesting a possible use of the model as part of the battery, representing the aggressive facet of mania. The second approach is based on identifying behavioral differences between existing strains of animals and identifying strains that may have a behavioral phenotype that resembles aspects of BPD. A similar approach has been used previously to model other psychiatric disorders and can be utilized for BPD research. An example of this possible approach is shown with the Black Swiss mice strain that appears to have more manic-like behaviors compared to other strains. Both approaches will not culminate to an ideal, all encompassing model of BPD but may provide useful and relatively uncomplicated tools for research of the disorder.