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The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
Antidepressant-like effect of oleanolic acid in mice exposed to the repeated forced swimming test
1Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, PR China. litao.yi@yahoo.com
Abstract:
The study aimed to explore the antidepressant-like effect of oleanolic acid and its possible mechanism related to the monoaminergic system and neurotrophin in mice exposed to the repeated forced swimming test (FST). Both the duration and the latency of immobility affected by oleanolic acid (10, 20 and 40 mg/kg) were evaluated in the FST repeated at intervals on days 1, 7 and 14, followed by neurochemical and brain-derived neurotrophic factor (BDNF) analyses in the mouse brain regions of frontal cortex and whole hippocampus. A repeated analysis of variance (ANOVA) indicated that over retesting the immobility time increased, whereas latency to immobility tended to decrease. Minute-by-minute analysis showed that immobility time also increased during the 4-min course of the test. In addition, post-hoc Dunnett's test demonstrated that sub-chronic and chronic, but not acute, oleanolic acid treatment reduced the immobility time (sub-chronic: 20 mg/kg, 43.5%; chronic: 10 mg/kg, 19.3%; 20 mg/kg, 31.8%) and increased the latency to immobility (sub-chronic: 10 mg/kg, 60.6%; 20 mg/kg, 80.1%; chronic: 10 mg/kg, 121.8%; 20 mg/kg, 140.8%; 40 mg/kg, 80.0%). Furthermore, chronic administration of oleanolic acid significantly increased serotonin (5-HT) levels (frontal cortex: 44.5%, 41.9%, 27.5% for 10, 20, 40 mg/kg; hippocampus: 57.2%, 80.9% for 10, 20 mg/kg), decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio (frontal cortex: 31.6%, 30.1%, 23.5%; hippocampus: 40.6%, 47.7%, 29.2% for 10, 20, 40 mg/kg) and elevated norepinephrine (NE) levels (hippocampus: 20 mg/kg, 45.4%) but did not alter dopamine (DA) levels. Moreover, BDNF levels in the two brain regions were also elevated by chronic oleanolic acid treatment (frontal cortex: 20 mg/kg, 67.2%; hippocampus: 10 mg/kg, 36.4%; 20 mg/kg, 55.1%). Taken together, these findings imply that functions of 5-HT, NE and BDNF may be involved in the antidepressant-like effect of oleanolic acid.
Insights
Oleanolic acid exhibits antidepressant-like effects in mice, reducing immobility time and increasing latency in the forced swimming test. Its mechanism involves modulating serotonin, norepinephrine, and brain-derived neurotrophic factor (BDNF) levels.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Depression is a prevalent mood disorder with complex pathophysiology.
- The monoaminergic system and neurotrophic factors, like brain-derived neurotrophic factor (BDNF), are implicated in depression.
- Oleanolic acid, a natural triterpenoid, has shown potential therapeutic properties.
Purpose of the Study:
- To investigate the antidepressant-like effects of oleanolic acid in a mouse model.
- To elucidate the underlying mechanisms involving the monoaminergic system and BDNF.
Main Methods:
- Mice were subjected to a repeated forced swimming test (FST) after administration of oleanolic acid (10, 20, 40 mg/kg).
- Behavioral parameters (immobility time, latency) were assessed.
- Neurochemical analyses of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), and dopamine (DA) were performed.
- Brain-derived neurotrophic factor (BDNF) levels were measured in the frontal cortex and hippocampus.
Main Results:
- Sub-chronic and chronic oleanolic acid treatment significantly reduced immobility time and increased latency in the FST.
- Chronic administration elevated serotonin and norepinephrine levels, and decreased the 5-HIAA/5-HT ratio in specific brain regions.
- BDNF levels were significantly increased in the frontal cortex and hippocampus following chronic oleanolic acid treatment.
- Dopamine levels remained unaltered.
Conclusions:
- Oleanolic acid demonstrates significant antidepressant-like effects in mice, particularly with sub-chronic and chronic administration.
- The antidepressant-like action of oleanolic acid is associated with the modulation of the 5-HT and NE systems, as well as increased BDNF levels.
- These findings suggest oleanolic acid as a potential therapeutic agent for depression.
