We published a paper, titled “Anxiety-like behaviors in mice unmasked: revealing sex differences in anxiety using a novel light-heat conflict test,” in Journal of Neuroscience Research! (pdf here) The study was led by a former graduate student from the lab, Dr. Sydney Lee.
Anxiety is twice as prevalent in women, yet sex differences for anxiety-like behaviors are not detected in rodents using commonly used tests.
In this paper, we develop a new test with two chambers that places an anxiety-inducing stimulus—light—in conflict with heat. The dark chamber floor heats to uncomfortable temperatures, whereas the illuminated chamber temperature remains comfortable. The test is called the Thermal Increments Dark-Light (TIDAL) conflict test.
Our data reveal that females remain on the dark-heating plate for longer than males, suggesting that females display increased anxiety-like behavior.
These anxiety-like behaviors in females were reduced using an anxiety-relieving drug, paroxetine. Since paroxetine reduced mouse preference for the dark-heated plate, this supports the premise that the TIDAL conflict test is a valid test for anxiety-like behavior.
Study summary: Tests for mouse anxiety-related behavior do not reliably recapitulate sex differences in human anxiety. The TIDAL conflict test comprises one dark plate that heats to uncomfortable temperatures, and one illuminated-isothermic plate. Female mice persist on the dark-heated plate longer than males; thus, TIDAL reveals clinically-relevant sex differences in anxiety-related behavior.
Therefore, the new TIDAL conflict test unmasks sex differences in mouse anxiety-like behavior - female mice displayed higher anxiety-like behavior than males, which recapitulates sex differences in anxiety observed in humans. Thus, the TIDAL conflict test could help identify new sex-specific mechanisms and treatments for anxiety.
Our prior work used the TIDAL conflict test to reveal that spinal cord injury in female and male mice induces robust anxiety-like behavior (pdf here). Thus, in addition to unveiling sex-specific mechanisms of anxiety, the TIDAL conflict test will be useful for exploring the relative salience of anxiety vs. heat sensitivity under pathological conditions - e.g., sickness, aging, or neurologic disorders.
Authors on the paper include Sydney Lee, Sung-Hoon Park, John Aldrich, Laura Fonken, and Andrew Gaudet. We appreciate support provided by University of Texas at Austin start-up funds, the Wings for Life Foundation, and Mission Connect, a program of the TIRR Foundation. Research was also supported by NIH NINDS R01NS131806 (Gaudet), and by NIH R01AG062716 (Fonken) and R01AG078758 (Fonken).