A “bipolar mouse” is an animal model developed to study the biological and genetic underpinnings of human bipolar disorder. These are not naturally occurring animals; they are created by scientists to exhibit characteristics that resemble the disorder’s symptoms. Researchers use these models to investigate complex causes and to explore potential new treatments, gaining insights impossible in human subjects.
Developing Animal Models for Bipolar Disorder
There is no single type of bipolar mouse; scientists employ several methods to create models that reflect different aspects of the disorder. One approach is genetic manipulation of specific genes linked to bipolar disorder in human studies. For example, the gene ANK3 has been identified as a risk factor. Scientists have created mice with altered ANK3 genes, which then display behaviors like hyperactivity and shifts between manic-like and depressive-like states.
Another genetic target is the CLOCK gene, which is integral to regulating circadian rhythms. Since disruptions in sleep are common triggers for manic episodes in humans, altering this gene in mice can produce hyperactivity and a reduced need for sleep. Similarly, genes related to the dopamine transporter (DAT) have been manipulated. Mice with reduced DAT function show behaviors that mimic aspects of mania, which is relevant as lower DAT levels are seen in some human studies.
A different strategy is pharmacological induction, which involves administering drugs to mice to induce states that resemble human symptoms. Psychostimulants like amphetamines are used because they can produce hyperactivity in rodents, a behavior that serves as an analogue for mania. This approach allows researchers to study the brain states associated with manic-like behaviors without a genetic component.
Observing Bipolar-Like Behaviors
Scientists measure a range of behaviors in these mouse models that correspond to the symptoms of mania and depression. For manic-like states, researchers observe increased locomotor activity, where mice move around more than typical mice. They also exhibit reduced anxiety and increased risk-taking, which can be measured in standardized tests like the elevated plus maze.
To quantify these behaviors, specific laboratory tests are used. The open field test is a common method where a mouse is placed in a large, empty box and its movements are tracked to measure hyperactivity. Another behavior associated with mania is a reduced need for sleep, which can be monitored by placing mice on a small platform over water, forcing them to stay awake.
Depressive-like behaviors are also assessed through established protocols. The forced swim test is widely used, where a mouse is placed in a container of water from which it cannot escape. A state analogous to depression is inferred if the mouse becomes immobile. Another indicator is anhedonia, a lack of interest in rewards, measured by whether a mouse chooses sugar water over plain water. Social withdrawal is also tracked by monitoring interaction with other mice.
Research Applications and Discoveries
These animal models are used in the development and screening of new medications. Before a potential drug is tested in humans, it is often evaluated in these models to see if it can reduce manic-like or depressive-like behaviors. For example, lithium, a common mood stabilizer, has been shown to reduce hyperactivity in some mouse models. This provides a platform for testing novel compounds.
Studying the brains of these mice provides insights into the neurobiology of mood regulation. By examining the neural circuits and neurotransmitter systems, scientists can identify which parts of the brain are involved. Research points to neurotransmitters like dopamine and serotonin, and models with altered dopamine transporters help clarify how dopamine signaling contributes to manic-like behaviors.
These investigations allow researchers to explore molecular and cellular mechanisms that are otherwise inaccessible in humans. Scientists can study changes in gene expression, protein levels, and neuronal activity in specific brain regions. For instance, research on mice with altered FADS genes, which are involved in fatty acid metabolism, has linked changes in omega-3 fatty acids to mood swings. This work helps build a foundational understanding of the disorder.
Relevance to Human Bipolar Disorder
Findings from mouse models must be carefully interpreted, as a mouse cannot fully replicate the complex human experience of bipolar disorder. Subjective feelings, intricate thought processes, and the social context of the human condition cannot be reproduced in an animal. The models are not a perfect copy but are designed to mimic specific, measurable components like hyperactivity or genetic predispositions.
Despite these differences, these models are valuable for investigating the underlying biology in a controlled environment. Humans have complex genetic and environmental backgrounds that make it difficult to isolate the disorder’s cause. In mouse models, scientists can control these variables and manipulate single genes to observe the direct effects on behavior and brain function.
This controlled approach provides foundational knowledge that guides research in humans. By identifying specific genes, brain circuits, and molecular pathways in mice, researchers can then look for similar mechanisms in human patients. The animal models help pinpoint areas for investigation, complementing human studies for a more complete picture of bipolar disorder.