Mutant Mouse Models of Bipolar Disorder.

Bipolar disorder (also known as manic-depressive illness) is distinctive among psychiatric illnesses in that it is characterized by spontaneously alternating episodes of depression and mania. Over the years, extensive research into the pathophysiology of bipolar disorder has resulted in a growing understanding of the cellular, biochemical, and molecular changes associated with bipolar disorder and its treatment. However, given its unique nature, developing an animal model for bipolar disorder in which all aspects of the illness are emulated is challenging. Indeed, fully validated animal models of bipolar disorder are not available and a variety of models are used to represent a single manic or depressive episode, with some models possibly representing the progressive nature of the disorder. Nonetheless, targeted mutations of specific neurotransmitter systems, including receptors and transporters, as well as genetic manipulations of cellular signaling pathways, produce a variety of changes in affective-like behavior, with most changes consistent with manic-like behavior. As such, these mutant mouse models (with their own limitations) could contribute to the research of the underlying brain mechanisms of mania and/or bipolar disorder. In this chapter, we present an overview of neurochemical, neuroendocrine, and behavioral changes in bipolar disorder, and of the available mutant mouse models in which some aspects of the disorder are emulated. The mutant mouse models include targeted overexpression or knockout/knock-down of genes coding for corticotropin-releasing factor, glucocorticoid receptor, serotonin transporters, and dopamine transporters, and of genes involved in intracellular signaling pathways. [ABSTRACT FROM AUTHOR]