Animal models for bipolar disorder: from bedside to the cage

Bipolar disorder is characterized by recurrent manic and depressive episodes. Patients suffering from this disorder experience dramatic mood swings with a wide variety of typical behavioral facets, affecting overall activity, energy, sexual behavior, sense of self, self-esteem, circadian rhythm, cognition, and increased risk for suicide. Effective treatment options are limited and diagnosis can be complicated. To overcome these obstacles, a better understanding of the neurobiology underlying bipolar disorder is needed. Animal models can be useful tools in understanding brain mechanisms associated with certain behavior. The following review discusses several pathological aspects of humans suffering from bipolar disorder and compares these findings with insights obtained from several animal models mimicking diverse facets of its symptomatology. Various sections of the review concentrate on specific topics that are relevant in human patients, namely circadian rhythms, neurotransmitters, focusing on the dopaminergic system, stressful environment, and the immune system. We then explain how these areas have been manipulated to create animal models for the disorder. Even though several approaches have been conducted, there is still a lack of adequate animal models for bipolar disorder. Specifically, most animal models mimic only mania or depression and only a few include the cyclical nature of the human condition. Future studies could therefore focus on modeling both episodes in the same animal model to also have the possibility to investigate the switch from mania-like behavior to depressive-like behavior and vice versa. The use of viral tools and a focus on circadian rhythms and the immune system might make the creation of such animal models possible.