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Updated: Jul 9, 2026
A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Mice that under- or overexpress glucocorticoid receptors as models for depression or posttraumatic stress disorder
Sabine Chourbaji1, Miriam A Vogt, Peter Gass
1Central Institute of Mental Health, J 5, D-68159, Mannheim, Germany.
Abstract:
Modern molecular and pathophysiological concepts suggest that glucocorticoid receptors (GRs) play a crucial role for the pathogenesis, course and therapy of affective or emotional disorders. Specifically, an impairment of GR signaling has been associated with major depression, whereas overactivity or hyperresponsiveness of GRs have been conceptualized for posttraumatic stress disorder (PTSD). Recently, several research groups have generated transgenic mouse strains that under- or overexpress GRs, respectively. These animals seem to represent valuable tools for studying the foregoing hypotheses. Indeed, first results indicate that mice with a deficit in GR expression show a depression-like behavioral phenotype as well as characteristic neuroendocrinological changes observed in depressive patients. Particularly, GR heterozygous mice with a 50% reduction of GR expression represent a model for combined effects of both genetic and environmental manipulations, since their depression-like behavior becomes only manifest after stress-exposure. Thus, the phenotype of this strain mimics the human situation in depressive disorders, in which individuals at risk are predisposed to develop depressive episodes after stress. It is currently less clear whether, and in which way, mice that overexpress GRs can serve as models for PTSD, or mimic at least specific aspects of the clinical syndrome. The latter strains have still to be subjected to specific tests analyzing conditioning and sensitization processes in fearful situations. So far, mice with compromised GR expression seem to be a good tool to further study molecular, pathophysiological and cellular/structural alterations that underlie specific behavioral features such as despair or helplessness. A major challenge is to decipher which signs and symptoms in patients correspond to these animal behavioral constructs, and to elucidate whether it is possible to gain insights from the animals' response to specific treatments for human therapy.
Insights
Glucocorticoid receptors (GRs) are key in emotional disorders. Mice with reduced GR expression show depression-like behaviors, especially after stress, modeling human depression risk.
Area of Science:
- Neuroscience
- Endocrinology
- Psychiatry
Background:
- Glucocorticoid receptors (GRs) are implicated in the development, progression, and treatment of emotional disorders.
- Impaired GR signaling is linked to major depression, while GR overactivity is hypothesized for posttraumatic stress disorder (PTSD).
- Transgenic mouse models with altered GR expression offer tools to investigate these hypotheses.
Purpose of the Study:
- To evaluate the utility of transgenic mouse models with modified GR expression for studying affective disorders.
- To explore the relevance of GR deficits and overactivity in modeling depression and PTSD.
- To understand the molecular and pathophysiological underpinnings of GR-related behavioral phenotypes.
Main Methods:
- Generation of transgenic mouse strains with either reduced or overexpressed GRs.
- Phenotypic analysis of these mouse models, including behavioral tests and neuroendocrinological assessments.
- Assessment of depression-like behaviors and stress-induced responses in GR-deficient mice.
Main Results:
- Mice with GR deficits exhibit depression-like behaviors and neuroendocrine changes mirroring those in human depression.
- GR heterozygous mice (50% GR reduction) display stress-dependent depression-like phenotypes, modeling human vulnerability.
- The utility of GR-overexpressing mice as models for PTSD requires further investigation, particularly regarding fear conditioning.
Conclusions:
- Mice with compromised GR expression are valuable tools for studying the molecular, pathophysiological, and cellular alterations in depression.
- GR heterozygous mice serve as a relevant model for the interplay of genetics and environment in depression.
- Further research is needed to correlate animal behavioral constructs with human symptoms and to explore therapeutic implications.
