Related Experiment Video
Updated: Jun 1, 2026
Animal Models of Depression - Chronic Despair Model (CDM)
Published on: September 23, 2021
Roles of exogenous and endogenous FGF-2 in animal models of depression
J Jarosik1, B Legutko, S Werner
1Interdisciplinary Center for Neurosciences (IZN), Department of Neuroanatomy, Heidelberg, Germany.
Purpose:
Several members of the fibroblast growth factor (FGF) family have been shown to be dysregulated in individuals with major depression, and treatment with antidepressants has been reported to increase FGF-2 mRNA levels in the forebrain.
Methods:
We have used the tail suspension test (TST), and olfactory bulbectomy (OBX), and FGF-2 deficient mice to investigate putative roles of FGF-2 as an antidepressant and mediator of antidepressive drug actions.
Results:
FGF-2 applied intraventricularly generated antidepressant-like effects in the TST. FGF-2, similar to the antidepressant amitriptyline, attenuated neuron demise in the piriform cortex and posterolateral cortical nucleus of the amygdala following OBX. Moreover, OBX induced reduction in hippocampal neurogenesis could be ameliorated by subsequent treatment with either amitriptyline or FGF-2. Furthermore, FGF-2 was effective in reversing depressive-like behavior induced by OBX, monitored in the locomotor activity and the passive avoidance test. In bulbectomized FGF-2 deficient mice, treatment with amitriptyline protected neurons, but failed to reverse behavioral alterations.
Conclusions:
Together, these results suggest that FGF-2 constitutes both a potential target for antidepressive treatments and an important growth factor in the cytokine network underlying the actions of antidepressive drugs. The results further suggest a requirement of endogenous FGF-2 for mediating behavioral, but not neuroprotective actions of amitriptyline.
Insights
Fibroblast growth factor-2 (FGF-2) shows antidepressant-like effects and mediates antidepressant actions. Endogenous FGF-2 is required for behavioral improvements from antidepressants, but not neuroprotection.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Dysregulation of fibroblast growth factor (FGF) family members is observed in major depression.
- Antidepressant treatments may increase FGF-2 mRNA levels in the brain.
Purpose of the Study:
- Investigate the role of FGF-2 as an antidepressant.
- Explore FGF-2's role in mediating antidepressant drug actions.
Main Methods:
- Utilized tail suspension test (TST), olfactory bulbectomy (OBX), and FGF-2 deficient mice.
- Administered FGF-2 intraventricularly and amitriptyline.
- Assessed neuroprotection, neurogenesis, locomotor activity, and passive avoidance.
Main Results:
- Intraventricular FGF-2 demonstrated antidepressant-like effects in the TST.
- FGF-2 and amitriptyline attenuated OBX-induced neuronal loss and reduced hippocampal neurogenesis.
- FGF-2 reversed OBX-induced depressive-like behaviors.
- Amitriptyline protected neurons in FGF-2 deficient mice but did not reverse behavioral deficits.
Conclusions:
- FGF-2 is a potential therapeutic target for depression and a key mediator in antidepressant drug action.
- Endogenous FGF-2 is essential for the behavioral effects of antidepressants, but not their neuroprotective actions.
