Bipolar disorder (BD) is a severe mental disorder that affects approximately 1–2% of the population worldwide. The age of onset for this debilitating disorder is approximately 20 years of age, and there is a high rate of suicide attempts associated with BD. Individuals diagnosed with BD may experience significant levels of disability over the lifespan. The heritability of BD is extremely high, with estimates up to 85%, and the genetic architecture is quite complex, with many risk genes thought to be involved, each contributing a small effect. There is also considerable evidence to support a powerful role for environmental factors interacting with these risk genes at different stages of development, including prenatal maternal infections, traumatic experiences in childhood, drug use and abuse, and stressful life experiences. Patients with BD often express co-morbidities for other psychiatric disorders, including attention deficit hyperactivity disorder, anxiety disorders, and substance use disorders [1].

The accidental discovery of lithium for the treatment of BD was first reported by Australian psychiatrist John Cade [2]. Since that time, breakthroughs in the pharmacological treatment of BD have been few and far between. One reason for the relative absence of targeted therapies for BD has been the difficulty in developing valid animal models. Two features of BD that are especially relevant for those interested in modeling this disorder in laboratory animals include the process of switching from a manic or hypomanic episode to depression (or vice versa), and the possible disruption of circadian systems in bipolar individuals, including alterations in sleep-wake patterns and seasonal variations in susceptibility to the onset of mania or bipolar depression. What is clear at this time is that the underlying neural and molecular mechanisms that regulate the switch process are incompletely understood in BD patients, and there is an urgent need for animal models that permit a detailed exploration of these underlying mechanisms.

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