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Updated: Jun 14, 2025

The Forced Swim Test as a Model of Depressive-like Behavior

The Forced Swim Test as a Model of Depressive-like Behavior

Published on: March 2, 2015

Icariin mitigates depressive-like behavior in rats by regulating mitochondrial function.

Hui Zhao¹, Sisi Zhang², Zheng Gong³

¹Institute of Maternal and Infant Health, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China; Clinical Experimental Center, Northwest University Affiliated Xi'an International Medical Center Hospital, Xi'an, 710100, China.

Journal of Ethnopharmacology

|May 27, 2025

Summary

Icariin (ICA) alleviates depression-like behaviors in prenatal stress rats by improving mitochondrial function and neuronal health. This traditional Chinese medicine component enhances synaptic plasticity and reduces neuronal apoptosis.

Keywords:

Depression Icariin Mitochondrial biogenesis Mitochondrial dynamics Mitophagy Prenatal stress

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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice

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Area of Science:

Neuroscience
Pharmacology
Mitochondrial Biology

Background:

Epimedii Folium, a traditional Chinese medicine, has historical uses for treating depression.
Icariin (ICA) is the primary active flavonoid in Epimedii Folium.

Purpose of the Study:

To elucidate the mechanisms by which Icariin (ICA) ameliorates depressive-like behaviors in prenatal stress (PS) offspring rats.
Investigate the impact of ICA on hippocampal structure, synaptic plasticity, and mitochondrial function in PS rats.

Main Methods:

Utilized male offspring rats subjected to prenatal stress (PS).
Employed H&E staining, Nissl staining, ELISA, Western blot, immunofluorescence, and molecular docking.
Assessed hippocampal neuronal damage, synaptic protein expression, mitochondrial dynamics, and apoptosis.

Main Results:

ICA treatment significantly reduced depressive-like behaviors and hippocampal neuronal damage in PS rats.
Restored hippocampal synaptic plasticity, mitochondrial dynamics, morphology, ATP levels, and mitochondrial membrane potential (MMP).
Reversed PS-induced neuronal apoptosis, decreased mitochondrial biogenesis proteins, and activated the PINK1/Parkin mitophagy pathway.

Conclusions:

Icariin (ICA) demonstrates significant antidepressant effects in a rat model of prenatal stress.
These effects are mediated through the improvement of mitochondrial dynamics, biogenesis, and mitophagy in the hippocampus.
ICA normalizes synaptic plasticity and reduces neuronal apoptosis, offering a potential therapeutic strategy for depression.