Disruption of social behavior is a feature of many human disorders, including developmental, psychiatric, and neurodegenerative disorders1,2. Mouse models are used to gain insight into the pathogenesis of these disorders and to provide a platform for the preclinical testing of therapeutics. However, many assays for mouse social behavior are time-consuming to perform, require expensive equipment and/or video-tracking software to analyze, or have subjective scoring algorithms. In contrast, the tube test for social dominance is quick and simple to perform and requires no specialized equipment or video tracking. The assay has a binary win/lose outcome, making the interpretation of results straightforward.
The tube test for social dominance was developed by Lindzey and colleagues in an effort toassess social dominance in mice3. Since its development, the tube test has also been established as a way to assess within-cage social dominance hierarchies4. Tube test phenotypes correlate with other measures of social dominance like barbering, reward competition, and urine-making in male mice5. However, there are mixed results of the tube test and its correlation with competition for food and water access and aggression3,6,7. Importantly, tube test phenotypes correlate with other social phenotypes such as three-chamber sociability8,9.
An advantage of the tube test is that its anatomy is well-defined, making it particularly useful in various mouse models, including models of autism spectrum disorders and other diseases characterized by social deficits like frontotemporal dementia8,9,10,11,12,13,14,15,16. The medial prefrontal cortex (mPFC) is a key mediator of mouse tube test behavior6. Wang and colleagues showed that activity in the mPFC drives social dominance in mice6, and more recent data have refined this insight by showing that mediodorsal thalamic input to the prelimbic and anterior cingulate cortices drives social dominance17. Consistent with a key role for the mPFC in tube test social dominance, abnormalities in dendritic arbors, dendritic spines, glutamate receptors, and/or neuronal excitability, the mPFC has been associated with tube test abnormalities in rodent models of autism spectrum disorders15,18, frontotemporal dementia8,19, chronic stress20, and social isolation21.
Another key advantage of the tube test is the ability to test social dominance both before and after therapeutic intervention, as mouse social dominance in the tube test is stable over time, allowing repeated testing both before and after an experimental intervention6,8,22,23. One example of this comes from progranulin heterozygous (Grn+/−) mouse models of frontotemporal dementia caused by progranulin (GRN) mutations, a haploinsufficiency disease. Progranulin heterozygous mice have a social dominance deficit8. This tube test deficit can be reversed by restoring progranulin with either AAV-progranulin gene therapy22, or administration of anti-sortilin antibodies designed to reduce progranulin degradation23. These examples demonstrate the usefulness of the tube test in designing preclinical trials for dementia-related research.
This protocol provides basic methods for running the tube test between non-cagemates to assess differences between experimental groups, and between cagemates to assess within-cage social dominance hierarchies.