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Updated: May 23, 2026
The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
Antidepressant effects of fibroblast growth factor-2 in behavioral and cellular models of depression
Maha Elsayed1, Mounira Banasr, Vanja Duric
1Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT 06508, USA.
Background:
Basic and clinical studies report that the expression of fibroblast growth factor-2 (FGF-2) is decreased in the prefrontal cortex (PFC) of depressed subjects or rodents exposed to stress and increased following antidepressant treatment. Here, we aim to determine if 1) FGF-2/fibroblast growth factor receptor (FGFR) signaling is sufficient and required for mediating an antidepressant response behaviorally and cellularly; and 2) if the antidepressant actions of FGF-2 are mediated specifically by the PFC.
Methods:
The role of FGF-2 signaling in behavioral models of depression and anxiety was tested using chronic unpredictable stress (CUS)/sucrose consumption test (SCT), forced swim test (FST), and novelty suppressed feeding test (NSFT). We also assessed the number of bromodeoxyuridine labeled dividing glial cells in the PFC as a cellular index relevant to depression (i.e., decreased by stress and increased by antidepressant treatment).
Results:
Chronic FGF-2 infusions (intracerebroventricular) blocked the deficit in SCT caused by CUS. Moreover, the response to antidepressant treatment in the CUS/SCT and FST was abolished upon administration of an inhibitor of FGFR activity, SU5402. These results are consistent with the regulation of proliferating cells in the PFC, a portion of which are of oligodendrocyte lineage. Lastly, subchronic infusions of FGF-2 into the PFC but not into the dorsal striatum produced antidepressant-like and anxiolytic-like effects on FST and NSFT respectively.
Conclusions:
These findings demonstrate that FGF-2/FGFR signaling is sufficient and necessary for the behavioral, as well as gliogenic, actions of antidepressants and highlight the PFC as a brain region sensitive to the antidepressant actions of FGF-2.
Insights
Fibroblast growth factor-2 (FGF-2) signaling is crucial for antidepressant effects, acting specifically in the prefrontal cortex (PFC). This pathway is both sufficient and necessary for antidepressant-like behaviors and cellular changes.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Fibroblast growth factor-2 (FGF-2) expression is altered in depression and by antidepressant treatment.
- FGF-2 levels are reduced in the prefrontal cortex (PFC) in depression and stress models.
- Antidepressant treatments increase FGF-2 expression.
Purpose of the Study:
- To determine if FGF-2/fibroblast growth factor receptor (FGFR) signaling is sufficient and required for antidepressant responses.
- To investigate if FGF-2's antidepressant actions are specifically mediated by the PFC.
- To examine the cellular and behavioral effects of FGF-2 signaling in depression models.
Main Methods:
- Behavioral tests for depression and anxiety: chronic unpredictable stress (CUS)/sucrose consumption test (SCT), forced swim test (FST), novelty suppressed feeding test (NSFT).
- Assessment of glial cell proliferation in the PFC using bromodeoxyuridine labeling.
- Pharmacological inhibition of FGFR activity and localized FGF-2 infusions into the PFC and dorsal striatum.
Main Results:
- Chronic FGF-2 infusions prevented stress-induced deficits in the SCT.
- Inhibition of FGFR activity abolished the antidepressant response to treatment in CUS/SCT and FST.
- FGF-2 infusions into the PFC, but not the dorsal striatum, produced antidepressant-like and anxiolytic-like effects.
- These effects correlated with changes in glial cell proliferation in the PFC.
Conclusions:
- FGF-2/FGFR signaling is sufficient and necessary for antidepressant-like behavioral and gliogenic effects.
- The prefrontal cortex (PFC) is a key brain region mediating the antidepressant actions of FGF-2.
- These findings identify FGF-2/FGFR signaling as a critical target for antidepressant therapies.
