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Updated: Apr 3, 2026
The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
11-β hydroxysteroid type 1 knockout mice display an antidepressant-like phenotype in the forced swim test
David A Slattery1, Doncho P Uzunov1, John F Cryan1
11Neuroscience Research,Novartis Institutes for BioMedical Research,Novartis Pharma AG,Basel,Switzerland.
Objective:
11β-dehydroxysteroid dehydrogenase (HSD) types 1 and 2, enzymes are involved in the activation and inactivation of glucocorticoids in vivo, respectively. Indirect evidence implicates two enzymes in the aetiology of depression but no study has directly assessed the potential role of 11 β-HSD1 in animal tests.
Methods:
We assessed 11 β-HSD1 knockout mice in the forced swim test (FST), tail suspension test (TST) and for locomotor activity.
Results:
Genetic ablation of the 11β-HSD1 gene results in an antidepressant-like phenotype in the FST; the most widely utilised animal test of antidepressant activity, but not in the related TST. This may be related to the different biological substrates underlying these tests. The decreased FST immobility was not due to alterations in general activity.
Conclusions:
Taken together these results suggest that 11β-HSD1 may play an important role in depression-related behaviours and further studies are necessary to fully characterise its role in such behaviour.
Insights
Genetic knockout of 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) shows antidepressant-like effects in mice. This suggests 11β-HSD1 plays a role in depression-related behaviors.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- 11 beta-hydroxysteroid dehydrogenase (HSD) enzymes regulate glucocorticoid activity.
- 11β-HSD1 activates glucocorticoids, while 11β-HSD2 inactivates them.
- Previous indirect evidence linked these enzymes to depression etiology.
Purpose of the Study:
- To directly investigate the role of 11β-HSD1 in depression-related behaviors using animal models.
- To assess the effect of 11β-HSD1 gene ablation on behavioral tests indicative of antidepressant activity.
Main Methods:
- Utilized 11β-HSD1 knockout mice.
- Assessed behavioral phenotypes using the forced swim test (FST) and tail suspension test (TST).
- Measured locomotor activity to control for general motor function.
Main Results:
- Genetic deletion of 11β-HSD1 resulted in an antidepressant-like phenotype in the FST.
- No significant antidepressant-like effect was observed in the TST.
- The observed behavioral changes were not attributable to alterations in general locomotor activity.
Conclusions:
- 11β-HSD1 appears to play a significant role in depression-related behaviors.
- Further research is warranted to fully elucidate the function of 11β-HSD1 in these behaviors.
- Findings suggest 11β-HSD1 as a potential therapeutic target for depression.
