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Updated: Jun 12, 2026
Elevated Plus Maze for Mice
Published on: December 22, 2008
Behavioral evaluation of transgenic mice with CNS expression of IFN-alpha by elevated plus-maze and Porsolt swim test
Hua Zhang1, Zhanzhuang Tian, Jianping Wang
1Department of Pharmacology & Toxicology, University of Missouri-Kansas City School of Pharmacy, Kansas City, MO 64108, United States.
Abstract:
Chronic IFN-alpha treatment as an antiviral or anti-cancer therapy can lead to severe psychiatric complications, including depression and anxiety in patients. In many animal models of IFN-alpha-induced behavioral dysfunction, the opposite results have frequently been reported. In an attempt to overcome the limitation of pharmacological studies, IFN-alpha-transgenic mice with CNS-targeted expression of the IFN-alpha transgene were used to study depression and anxiety-like behaviors by Porsolt swim and elevated plus-maze assays, respectively. Interestingly, chronic stimulation of IFN-alpha signaling in mouse brains did not cause depression or anxiety as measured by these tests in comparison with wild-type littermates. This observation suggests that factors other than IFN-alpha may be necessary for the development of psychiatric complications following IFN-alpha therapy in patients.
Insights
Interferon-alpha (IFN-alpha) therapy can cause psychiatric issues. However, in IFN-alpha-transgenic mice, brain-targeted IFN-alpha signaling did not induce depression or anxiety-like behaviors.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Chronic interferon-alpha (IFN-alpha) therapy, used for antiviral and anti-cancer treatments, is associated with severe psychiatric complications like depression and anxiety in patients.
- Existing animal models often report contradictory findings regarding IFN-alpha's behavioral effects, limiting direct translation to human conditions.
Purpose of the Study:
- To investigate the direct impact of sustained central nervous system (CNS) IFN-alpha signaling on depression and anxiety-like behaviors.
- To overcome limitations of pharmacological studies by using a transgenic mouse model with targeted IFN-alpha expression in the brain.
Main Methods:
- Utilized IFN-alpha-transgenic mice with CNS-targeted expression of the IFN-alpha transgene.
- Assessed depression-like behavior using the Porsolt swim test.
- Evaluated anxiety-like behavior using the elevated plus-maze test.
- Compared behavioral outcomes with wild-type littermates.
Main Results:
- Chronic stimulation of IFN-alpha signaling within the mouse brain did not result in depression-like behaviors.
- No significant anxiety-like behaviors were observed in the IFN-alpha-transgenic mice compared to controls.
- These findings contrast with reported psychiatric complications in patients undergoing IFN-alpha therapy.
Conclusions:
- Central nervous system IFN-alpha signaling alone may not be sufficient to induce depression and anxiety.
- Factors beyond direct IFN-alpha action in the brain might be crucial for the development of psychiatric complications associated with IFN-alpha therapy.
- Further research is needed to identify other contributing factors in IFN-alpha-induced psychiatric dysfunction.
