Neurobiology of the switch in bipolar disorder-investigations in an animal model

• Applicant: Professorin Dr. Nadja Freund
• Subject Area: Biological Psychiatry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 552842155

Nearly 50 million people worldwide suffer from bipolar disorder. This affective disorder is characterized by episodes of mania and depression. Underlying neurobiological mechanisms are hardly known and therefore treatment options and early diagnosis criteria are rare and urgently needed. Animal models are a very useful tool to further investigate mechanisms in the brain related to psychiatric disorders. However, these models often focus on mania or depression but do not allow the investigation of the switch between episodes. We recently created a unique rat model by manipulating the dopaminergic system. Viral overexpression of the dopamine D1 receptor in the prefrontal cortex induces mania-like behavior that is followed by depressive-like behavior once the overexpression is terminated. One aim of the proposed study is to further validate this promising model. Tracking of motivational behavior and circadian rhythm over several weeks will allow us to further characterize the switch between episodes in this model. In addition, we will investigate if commonly used drugs to treat human patients, namely lithium and quetiapine, are able to prevent the switch. For the first time, the model will be applied not only in male but also in female rats to study potential hormonal effects. Furthermore, brain tissue will be analyzed to understand the mechanisms that lead to depressive-like behavior by the simple termination of dopamine D1 overexpression. Taken together, the proposed project will further develop and validate a rodent model for bipolar disorder that will give the unique opportunity to study the underlying neurobiology of the switch between episodes in bipolar disorder.

• DFG Programme: Research Grants