Selecting an appropriate stress model of depression in rodents

Table 1 Advantages and disadvantages of common depression model animal strains

Strains	Advantages	Disadvantages
C57BL/6	Maintain a state of chronic psychological stress	Little spontaneous activity
	More likely to exhibit depressive states	Poor ability to explore novel environments
	Little individual variation and high stability
BALB/c	Lower social performance	Poor motherhood, low litter size, and high mortality of litters
	Better replicates some models of psychosomatic illness in humans	Relatively low aggressiveness
	Besides showing emotional stress changes, it also shows qi deficiency-like symptoms, which is suitable for building a combined Chinese medicine disease and evidence model
Kunming breed	Only one experiment is needed to achieve the observation effect and the experiment cost is low	High variation in growth and reproduction in the presence of inconsistent genetic backgrounds
	Can be used for experiments on mental differences between genders
	Good reproducibility of experiments
Wistar Kyoto	Susceptibility to learned helplessness	High reactivity to stress is more likely to lead to anxiety-based mental illness
	Long duration of resting despair in the forced swim experiment
	Short activity distances also appear in the open field experiment
Sprague Dawley	Significant impairment of non-spatial learning memory capacity	No obvious disadvantages
	A marked depression-like profile is accompanied by a less pronounced anxiety-like presentation
Flinder Resistant Line	Very sensitive to a wide range of drugs with different pharmacological mechanisms	Antidepressant-like behaviour can occur with long-term medication
Wistar	This is an important guideline for the study of the “qi stagnation and blood stasis” model in Chinese medicine	Habitat reproduction patterns are easily influenced by the external environment

Table 2 Advantages and disadvantages of animal models of depression

Depression modeling approaches	Advantages	Disadvantages
Behavioral despair model	Fast model construction	Strain differences
	High success rate of model construction	Cannot evaluate the etiologic mechanism
	Low expenditure and manpower requirements	Possibility of false positive
	High predictive validity	Single stimulus source
	Can be used for the first screening of broad-spectrum antidepressants	Excessive irritation
Learned helplessness model	High face and predictive validity	Need to set up control groups
	More comprehensive simulation of depression symptoms	The duration of depressive behavior is short
	High repeatability	Need special equipment and complex conditions
	Imitates neural circuit alterations of depression	Strain differences
	Can be used to study the pathogenesis of depression	Easily affected by subjective impacts
	Can be used to screen depression susceptibility strains and susceptibility genes
Social defeat stress model	Superior face, construct, and predictive validity	Can produce symptoms of depression and anxiety at the same time
	Simulate human social situations	Can be confused with anxiety
	Produce organic and functional changes	Not applicable to females
	It can be used for screening long-term chronic antidepressants	Longer modeling duration
	Depressive behavior lasts for a long time
Chronic social isolation model	Superior face, construct, and predictive validity	Strain differences
	Simulate human social situations	Large variation in model animal behaviour
	Produce organic and functional changes	Lack of uniformity in the length and standard of model preparation
	Not limited by animal gender
Chronic unpredictable stress model	Great face, construct, and predictive validity	Longer modeling duration
	Can avoid the adaptive phenomenon caused by the repetition of a single stimulus	Heavy workload, waste of resources and labor
	Measures anhedonia	High stimulation and high animal mortality
	Can help simulate and find the risk factors of depression	Susceptible to environmental influences
	Can verify the efficacy of new antidepressants
	Can explore the gender differences of rodents under stress conditions
Chronic unpredictable mild stress model	Superior face, construct, and predictive validity	Low repeatability
	Depressive behavior lasts for a long time	Longer modeling duration
	The stimulation intensity is mild	Heavy workload, waste of resources and labor
	No lasting and irreversible effects on animals	Different strains have different sensitivity to stimulation intensity
	More in line with animal ethical requirements
	Stimulus is unpredictable
	Can supplement problems that other models cannot carry out
	Best suited for combination with other types of models or multi-method combinations of the same type
Chronic restraint stress model	Simple operation and strong repeatability	Single form of stimulus
	Non-invasive stimulation	Animals are prone to adaptation
	Can be used for the screening of anti-depression and anti-anxiety drugs	Can be confused with anxiety
	Can be used in combination with chronic unpredictable mild stress
Maternal separation model	Can improve the susceptibility of animals to other stresses (chronic unpredictable mild stress) after adulthood	Easily affected by environmental impacts
	Can explore the effect of early stress on the pathophysiology of offspring after adulthood	Strain differences
	Emotional and stress responses have long-term effects	Sex difference, and female animals show better sensitivity
	Stable phenotype
Sleep interruption model	Have the dual characteristics of sleep disorder and depression	Model intervention methods and standards are not uniform
	Can be used to study the comorbidity mechanism of depression and sleep problems	Validity of the model needs to be verified