Name: the forced swim test as a model of depressive-like behavior
Uploaded: 2015-03-02T15:00:00.000+00:00
Duration: 5 min 42 s
Description: Watch this Scientific Journal Video about The Forced Swim Test as a Model of Depressive-like Behavior at JoVE.com

This research was supported by the Israel Science Foundation (grant No. 738/11), by the National Institute for Psychobiology in Israel (NIPI-7-2011-12), and by the Open University Foundation

NOTE: All experimental protocols were approved by the International Committee for Animal Care and Use in Israel. All efforts were made to minimize the number of animals used and their suffering.
1. Preparation for the Forced Swim Test
<ol>
	<li>Use two adjacent rooms. Use one room as a &#8220;waiting room&#8221; for holding the animals prior to behavioral testing, and the other for carrying out the procedure.</li>
	<li>Prepare transparent cylindrical glass containers (the only restriction for the number of containers is the space available) measuring 50 cm in height and a diameter of 20 cm. 
	NOTE: It is possible to run several animals simultaneously in the same room. If so, separate the containers from one another using a dark screen so that the animals will not see each other during the procedure.</li>
	<li>Prepare video camera(s) in front of the containers so that every camera perceives one or more containers in a way that will allow the clear observation of the animals&#8217; behavior later on while viewing the footage.</li>
	<li>Prepare clean drying cages, heat lamps and heat pads for the animals that have finished the procedure to avoid hypothermia. Make sure the bottom of the cage has blotting paper and change it when it gets wet. Do not place the cages in the testing room. 
	NOTE: Make sure not to mix animals from different home cages while they are staying in the transient drying cages.</li>
</ol>
2. Animal Handling Prior to Testing
<ol>
	<li>House animals in a room with a 12 hr light/dark cycle.</li>
	<li>During the days of the experimental procedure give the animals free access to food and water, except for the specific time spent in the procedure room.</li>
	<li>When using rats, handle the animals for about 2 min daily, 5 days prior to the beginning of the experimental procedure.</li>
</ol>
3. Training Procedure
The procedure is carried out differently for rats and mice.
NOTE: For both mice and rats, watch the animals while they are in the water at all times. In case an animal appears in serious distress (e.g. very tired, cannot stay up float) remove the animal from the water and exclude it from the experiment.
<ol>
	<li>For mice &#8212; There is one session 6 min long, divided into pretest (the first 2 min) and test (the last 4 min).
	<ol>
		<li>In order for the mice to get acclimated to the testing environment, transport the animals in their home cages at least 30 min prior to behavioral testing to the waiting room.</li>
		<li>Fill the cylinders with tap water at 25 &#176;C and adjust the water depth according to the mouse&#8217; size, so that it cannot touch the bottom of the container with its hind legs.</li>
		<li>Mark the cylinder with the animal number for the purpose of the identification of the animal later on while viewing the footage.</li>
		<li>Turn on the video camera/s and then place each mouse in the water filled cylinder container for 6 min.</li>
		<li>After 6 min have elapsed, turn the camera/s off, remove the mouse from the container and place it in the transient drying cage with the heat lamp above it and the heat pad under it.&#160;The mice should be closely and continuously monitored while recovering in this cage. For this purpose it is possible to place a thermometer at the level of the mice to make sure the temperature in the cage does not exceed 37 &#176;C. Also, place the cage such that not all of it falls under the lamp or over the pad; this allows the mouse to move to a cooler area if desired.</li>
		<li>Change the water after every session to avoid any influence on the next mouse.</li>
	</ol>
	</li>
	<li>For rats &#8212; There are 2 sessions, 24 hr apart. The first session is the pre-test stage (15 min) and the second session is the test stage (5 min).
	<ol>
		<li>In order for the rats to get acclimated to the testing environment, transport the animals in their home cages at least 30 min prior to behavioral testing to the waiting room.</li>
		<li>Fill the cylinders with tap water at 23 &#177; 1 &#176;C and adjust the water depth according to the rat&#8217;s size, so that it cannot touch the bottom of the container with its hind legs.</li>
		<li>Mark the cylinder with the animal number for the purpose of the identification of the animal later on while viewing the footage.</li>
		<li>Place each rat in the water filled cylinder container for 15 min.</li>
		<li>After 15 min have elapsed remove the rat from the container and place it in the transient drying cage with the heat lamp above it and the heat pad under it.&#160;The rat should be closely and continuously monitored while recovering in this cage. For this purpose it is possible to place a thermometer at the level of the rat to make sure the temperature in the cage does not exceed 37 &#176;C. Also, place the cage such that not all of it falls under the lamp or over the pad; this allows the rat to move to a cooler area if desired.</li>
		<li>Change the water after every session to avoid any influence on the next rat. 
		NOTE: This is the end of the pretest stage.</li>
		<li>Twenty-four hours later, in order for the rats to get acclimated to the testing environment, transport the animals in their home cages at least 30 min prior to behavioral testing to the waiting room.</li>
		<li>Fill the cylinders with tap water at 23 &#177; 1 &#176;C and adjust the water depth according to the rat&#8217;s size, so that it cannot touch the bottom of the container with its hind legs.</li>
		<li>Mark the cylinder with the animal number for the purpose of the identification of the animal later on while viewing the footage.</li>
		<li>Turn on the video camera/s and then place the rat in the water filled cylinder container for 5 min. Make sure that each rat is tested in the same container and position in the room as the previous day.</li>
		<li>After 5 min have elapsed turn the camera/s off, remove the rat from the container and place it in the transient drying cage with the heat lamp above it and the heat pad under it.&#160;The rat should be closely and continuously monitored while recovering in this cage. For this purpose it is possible to place a thermometer at the level of the rat to make sure the temperature in the cage does not exceed 37 &#176;C. Also, place the cage such that not all of it falls under the lamp or over the pad; this allows the rat to move to a cooler area if desired.</li>
		<li>Change the water after every session to avoid any influence on the next rat. 
		NOTE: This is the end of the test stage.</li>
	</ol>
	</li>
</ol>
4. The Behavioral Coding
For mice, code the last 4 min defined as the test stage. For rats, code the 5 min of the test stage.
<ol>
	<li>Code the duration of time spent as &#8220;Immobile&#8221; if the mouse is floating with the absence of any movement except for those necessary for keeping the nose above water.</li>
	<li>Code the duration of time spent as &#8220;Struggling/climbing&#8221; if quick movements of the forelimbs are observed such that the front paws break the surface of the water.</li>
	<li>Code the duration of time spent as &#8220;Swimming&#8221; if movement of forelimbs or hind limbs in a paddling fashion is observed. 
	NOTE: It is possible to use an alternative way to code these behaviors, this includes a time-sampling method. Rate the swimming, struggling or immobility as the frequency of episodes at 5 sec intervals throughout the test session.</li>
</ol>

The authors have nothing to disclose.

The FST is used to monitor depressive-like behavior and is based on the assumption that immobility reflects a measure of behavioral despair 3. The main advantages of this procedure lie in its relatively easy operation and fast results. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity 29. Importantly, this test can also differentiate between drugs that are not aimed for the treatment of depression such as benzodiazepines, which have been shown to possess anti-anxiety effects 3,30. Another example of the value of the FST in the study of depression, which also contributes to its face validity, is the fact that models of predisposition to depression were found to influence the immobility behavior. For example, its use as a marker of depressive-like behavior in genetic research. Genetic animal models of depression have been successfully breeding rodents on the basis of their immobility in the FST 32, suggesting that immobility is determined by a heritable trait, although some strains have shown innately high immobility in the FST 33,34. Additionally, it is important to mention that genetic models that are not based on the performance in the FST were also found to be successful in providing valid models for studying depressive-like behavior 35,36. In addition to the genetic research, the immobility behavior in the FST has been shown to be influenced in several animal models that are linked with predisposition to depression, such as early exposure to stress 37,38, clinical diabetes 39,40 and acute drug withdrawal41.
Despite its appeal, reservations regarding its construct validity that cast doubt on it being a model for depression have also been raised. For example, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms 42-44. That raises the question of whether immobility in the FST and depression share the same long-term adaptive changes in neuronal circuitry that underlie the effects of antidepressants in humans. With that said, it is important to mention that several recent studies have shown effects of antidepressants in this test following chronic treatment at much lower doses than those needed to induce effects after acute augmentation 24,45. Another much-discussed issue is the precise meaning of the immobility behavior as a measure that reflects the symptoms of depression 18,25. It is important to note that the immobility in these tests seems to be the result of an inability or reluctance to maintain effort rather than a generalized hypoactivity. This is of special importance due to the fact that patients suffering from depression show psychomotor impairments, particularly in those tests requiring the duration of effort 46. The active behaviors in this model (i.e. struggling and swimming) could potentially lead to escape and as a result decrease stress, whereas the passive behavior (i.e. immobility) may preserve energy while waiting for a possible escape. The animal&#8217;s choice of behavior varies and depends on numerous factors (e.g. pre-exposure, energy status, treatment, etc.). SSRIs have shown to postpone the transition from active to passive coping strategies, whereas factors that were found associated with depression accelerate this transition 18. Moreover, few questions have been raised regarding immobility as a learned process, meaning that the animal might learn that the best solution would be to be passive and wait to be removed from the water, what has been described as learned immobility 47-49. However, one might claim that this view leads to an anthropomorphic perspective of this model. In addition, negative correlation between longer immobility duration and stress hormones was not found 50,51. Furthermore, SSRIs were found to reduce immobility in a single test session following chronic administration in rats 52 or even following acute administration in mice 29 suggesting that where SSRIs are concerned learned immobility does not seem to play a role.
Another important notion is the role of the active behaviors during the FST. Although immobility is the behavior that is usually presented in articles, the other two measures have also been shown to be significant. Specifically, antidepressants that increase serotonergic neurotransmission led to longer swimming durations whereas those that were found to increase catacholaminergic neurotransmission led to longer struggling durations 18. This may help us to differentiate the neurochemical mechanisms underlying this behavior in different experiments. This was observed mainly in rats 53-56 and may be the cause that in our results exposure to the SSRI escitalopram resulted in the increase of the struggling but not the swimming behavior.
In addition, due to the fact that some antidepressants are known for reducing locomotor activity 18 and also that drugs such as psychomotor stimulants were found to reduce immobility in the FST 18,20,31 but are not effective for treating depression, it is recommended to preform locomotor activity tests in addition to the FST to rule out that the basal activity level is not the determining factor in this model. Moreover, due the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure. Also when preforming a number of behavioral tests, if the other paradigms are not considered stressful, it is recommended that the FST will be the last assay that is carried out.
Last, although in the past the scoring in this procedure was submitted to the possibility of bias by the experimenter, it is becoming more and more common to use designated software that eliminates this disadvantage 12,57,58.

Depression is a life-threatening psychiatric disorder and a major public health concern worldwide with an incidence of 5% and a lifetime prevalence of 15-20%. Moreover, it is estimated that by 2020 depression will be in the top three contributors to the burden of disease1,2. Depression is associated with disability, decreased quality of life, increased health-related costs and is considered a main risk factor for many diseases, including cardiovascular, metabolic and neuropsychiatric disorders3,4.Current pharmaco-therapeutic treatments have limited efficacy and are associated with many deleterious side effects5,6. Therefore, a better understanding of the pathophysiology of this disorder alongside with the development of innovative and improved treatments remains crucial. Hence, animal models are essential for advancing research in this field.
There are many models used for the study of this disorder (e.g. sucrose preference test, tail suspension test) with the forced swimming test (FST, also known as Porsolt&#8217;s test after the developer of this model 7,8) being one of the most commonly used assays 7,9-12.
During the FST an animal is placed in a container filled with water from which it cannot escape. The animal will first try to escape but eventually will exhibit immobility (i.e. floating with the absence of any movement except for those necessary for keeping the nose above water). The FST is a very popular model in animal research for a number of reasons. First, it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression 12-14. Moreover depression is often viewed as a lack of ability to handle with stress 15-17. Second, pharmacological treatment with antidepressants prior to the test has been shown to reduce immobility in the FST 18-23. Therefore, it is often used as a screening assay for novel compounds with potential antidepressant properties 15-17,24. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, such as changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia 15-17,24. This is also the reason why this test is sometimes used to evaluate depressive-like behavior in mutant mice, with increase or decrease in basal immobility (compared to &#8216;wild-type&#8217; mice) 25,26.

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the forced swim test as a model of depressive-like behavior

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

The following results are based on unpublished data from our lab. In this experiment, adult ICR female mice were tested after 3 weeks of treatment with the selective serotonin reuptake Inhibitor (SSRI) escitalopram or novel herbal anti-depressive and anti-anxiety treatment (NHT) (for additional information regarding the herbal treatment, see 12,27,28). One-way ANOVA revealed that the treatment reduced depressive-like behavior in the FST [F(2,58) = 4.88, p &#60;0.05]. One-sided Dunnet analysis revealed that treatment with either escitalopram or the NHT reduced depressive-like behavior in the FST (see Fig. 1A for post hoc comparisons). The treatment also increased struggling behavior in the FST [F(2,58) = 4.36, p &#60;0.05]. One-sided Dunnet analysis revealed that treatment with escitalopram increased struggling behavior in the FST (see Figure 1B for post hoc comparisons). The treatment had no effect on swimming behavior [F(2,58) = 2.89, p &#62;0.05, Figure 1C].
<img alt="Figure 1" src="/files/ftp_upload/52587/52587fig1highres.jpg" /> 
Figure 1A: Representative results of the effects of the NHT and escitalopram treatment (3 weeks) on immobility time in the FST (N: NHT = 19, escitalopram = 19, control = 21). *p &#60;0.05, **p &#60;0.005.
<img alt="Figure 2" src="/files/ftp_upload/52587/52587fig2highres.jpg" /> 
Figure 1B: Representative results of the effects of the NHT and escitalopram treatment (3 weeks) on struggling time in the FST (N: NHT = 19, escitalopram = 19, control = 21). *p &#60;0.05, **p &#60;0.005.
<img alt="Figure 3" src="/files/ftp_upload/52587/52587fig3highres.jpg" /> 
Figure 1C: Representative results of the effects of the NHT and escitalopram treatment (3 weeks) on swimming time in the FST (N: NHT = 19, escitalopram = 19, control = 21).

Watch this Scientific Journal Video about The Forced Swim Test as a Model of Depressive-like Behavior at JoVE.com

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

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like ...

the-forced-swim-test-as-a-model-of-depressive-like-behavior

Nanyang Technological University

Research

JoVE Journal

Behavior

36.9K Views.  Tel-Aviv University. This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

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

A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of depression is essential. Because there are several types of depression, various animal models are needed for a deeper understanding of the disorder. Previously, a mouse model of subchronic and mild social defeat stress (sCSDS) using a modified chronic social defeat stress (CSDS) paradigm was established. In the paradigm, to reduce physical injuries from aggressors, the duration of physical contact between the aggressor and a subordinate was reduced compared to in the original CSDS paradigm. sCSDS mice showed increased body weight gain, food intake, and water intake during the stress period, and their social behaviors were suppressed after the stress period. In terms of the face validity of the stress-induced overeating and overdrinking following the increased body weight gain, the sCSDS mice may show some features related to atypical depression in humans. Thus, a mouse model of sCSDS may be useful for studying the pathogenic mechanisms underlying depression. This protocol will help establish the sCSDS mouse model, especially for studying the mechanisms underlying stress-induced weight gain and polydipsia- and hyperphagia-like symptoms.

Here, methods for developing a mouse model of subchronic and mild social defeat stress are described and used to investigate the pathogenic features of depression including hyperphagia- and polydipsia-like symptoms following increased body weight.

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of ...

The Mouse Forced Swim Test

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed.

The forced swim test is validated as an experimental approach to assess potential antidepressant efficacy in rodents. Experimental animals are placed in a tank of water and escape-related mobility behavior is quantified. The common procedures for the mouse version of this test are described.

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental ...

Neuroscience

A New Method for Inducing a Depression-Like Behavior in Rats

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is no existing format for studying the mechanism of action, prevention, containment, and treatment of contagious depression. The purpose of this study, therefore, was to establish the first animal model of contagious depression.
Healthy rats can contract depressive behaviors if exposed to depressed rats. Depression is induced in rats by subjecting them to several manipulations of chronic unpredictable stress (CUS) over 5 weeks, as described in the protocol. A successful sucrose preference test confirmed the development of depression in the rats. The CUS-exposed rats were then caged with na&#239;ve rats from the contagion group (1 na&#239;ve rat/2 depressed rats in a cage) for an additional 5 weeks. 30 social groups were created from the combination of CUS-exposed rats and na&#239;ve rats.
This proposed depression-contagion protocol in animals consists mainly of cohabiting CUS-exposed and healthy rats for 5 weeks. To ensure that this method works, a series of tests are carried out - first, the sucrose preference test upon inducing depression to rats, then, the sucrose preference test, alongside the open field and forced-swim tests at the end of the cohabitation period. Throughout the experiment, rats are given tags and are always returned to their cages after each test.
A few limitations to this method are the weak differences recorded between the experimental and control groups in the sucrose preference test and the irreversible traumatic outcome of the forced swim test. These may be worth considering for suitability before any future application of the protocol. Nonetheless, following the experiment, na&#239;ve rats developed contagion depression after 5 weeks of sharing the same cage with the CUS-exposed rats.

This protocol describes a new model by which healthy rats could contract depression over a given time periodthrough contagion by exposure to chronic unpredictable stressed (CUS) rats.

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is ...

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by many patients prompts the need to develop new therapeutic alternatives and to better understand the etiology of the disorder. Pre-clinical models with translational merits are rudimentary for this task. Here we present a protocol for the unpredictable chronic mild stress (UCMS) method in mice. In this protocol, adolescent mice are chronically exposed to interchanging unpredictable mild stressors. Resembling the pathogenesis of depression in humans, stress exposure during the sensitive period of mice adolescence instigates a depressive-like phenotype evident in adulthood. UCMS can be used for screenings of antidepressants on the variety of depressive-like behaviors and neuromolecular indices. Among the more prominent tests to assess depressive-like behavior in rodents is the sucrose preference test (SPT), which reflects anhedonia (core symptom of depression). The SPT will also be presented in this protocol. The ability of UCMS to induce anhedonia, instigate long-term behavioral deficits and enable reversal of these deficits via chronic (but not acute) treatment with antidepressants strengthens the protocol&#39;s validity compared to other animal protocols for inducing depressive-like behaviors.

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by ...

Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice

In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall improvement of patients with major depressive disorder (MDD). Therefore, the purpose of this study was to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and then evaluate the anti-depression effect of Xiaoyaosan. Mice were randomly divided into four groups: a control group, a model group, a treatment group with Xiaoyaosan, and a treatment group with fluoxetine. All mice were individually kept in cages, and depression was induced in the mice by exposing them to several designed manipulations of CUMS for 21 days, as described in the protocol. Mice in the control group and model group received 0.5 mL of distilled water, while mice in the treatment groups received either Xiaoyaosan (0.25 g/kg/day) or fluoxetine (2.6 mg/kg/day). The drugs used in the study were given intragastrically daily during the entire three weeks. To estimate the depressive-like behaviors, a series of parameters including the coat state, body weight, open field test score, and sucrose preference test score were recorded. Data analysis showed that behaviors of model mice were significantly changed compared to behaviors of mice in the control group, which were improved by the treatment of Xiaoyaosan and fluoxetine. The current findings demonstrated the anti-depression effects of Xiaoyaosan on the behaviors of CUMS-induced mice and revealed that compounds from the Xiaoyaosan prescription may be worthwhile for treating depression, considering their beneficial effects on depressive-like behaviors.

Here, we present a protocol to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and evaluate the anti-depression effect of Xiaoyaosan.

In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall ...

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and ...

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

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, therapeutic treatments for depression or research on depression is scarce. Thus, in the present paper, we propose a mouse model of depression induced by movement restriction. Chronic mild stress (CMS) is a well-known technique to induce depressive-like behavior. However, it necessitates a complex procedure consisting of a combination of various mild stresses. In contrast, chronic immobilization stress (CIS) is a readily accessible chronic stress model, modified from a restraint model that induces depressive behavior by restricting movement using a restrainer for a certain period. To evaluate the depressive-like behaviors, the sucrose preference test (SPT), the tail suspension test (TST), and the ELISA assay to measure stress marker corticosterone levels are combined in the present experiment. The described protocols illustrate the induction of CIS and evaluation of the changes in behavior and physiological factors for the validation of depression.

This article provides a simplified and standardized protocol for induction of depressive-like behavior in chronically immobilized mice by using a restrainer. In addition, behavior and physiological techniques to verify induction of depression are explained.

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, ...

A Chronic Sleep Fragmentation Model using Vibrating Orbital Rotor to Induce Cognitive Deficit and Anxiety-Like Behavior in Young Wild-Type Mice

Sleep disturbance is generally common in populations as a chronic disease or a complained event. Chronic sleep disturbance is proposed to be closely linked to the pathogenesis of diseases, especially neurodegenerative diseases. We recently found that 2 months of sleep fragmentation initiated Alzheimer&#8217;s disease (AD)-like behavioral and pathological changes in young wild-type mice. Herein, we present a standardized protocol to achieve chronic sleep fragmentation (CSF). Briefly, CSF was induced by an orbital rotor vibrating at 110 rpm and operating with a repetitive cycle of 10 s-on, 110 s-off, during light-ON phase (8:00 AM&#8211;8:00 PM) continuously for up to 2 months. Impairments of spatial learning and memory, anxiety-like but not depression-like behavior in mice as consequences of CSF modeling, were evaluated with Morris water maze (MWM), Novel object recognition (NOR), Open field test (OFT) and Forced swimming test (FST). In comparison with other sleep manipulations, this protocol minimizes the handling labors and maximizes the modeling efficiency. It produces stable phenotypes in young wild-type mice and can be potentially generated for a variety of research purposes.

Presented here is a protocol for chronic sleep fragmentation (CSF) model achieved by an electrically controlled orbital rotor, which could induce confirmed cognitive deficit and anxiety-like behavior in young wild-type mice. This model can be applied to explore the pathogenesis of chronic sleep disturbance and related disorders.

Sleep disturbance is generally common in populations as a chronic disease or a complained event. Chronic sleep disturbance is proposed to be closely ...

Animal Models of Depression - Chronic Despair Model (CDM)

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. Despite its importance, current pharmacological treatment is limited, and novel treatment options are urgently needed. One key factor in the search for potential new drugs is evaluating their anti-depressive potency in appropriate animal models. The classical Porsolt forced swim test was used for this purpose for decades to induce and assess a depressive-like state. It consists of two short periods of forced swimming: the first to induce a depressed state and the second on the following day to evaluate the antidepressant effect of the agent given in between the two swim sessions. This model might be suitable as a screening tool for potential antidepressive agents but ignores the delayed onset of action of many antidepressants. The CDM was recently established and represented a modification of the classical test with notable differences. Mice are forced to swim for 5 consecutive days, following the idea that in humans, depression is induced by chronic rather than by acute stress. In a resting period of several days (1-3 weeks), animals develop sustained behavioral despair. The standard read-out method is the measurement of immobility time in an additional delayed swim session, but several alternative methods are proposed to get a broader view of the mood status of the animal. Multiple analysis tools can be used targeting behavioral, molecular, and electrophysiological changes. The depressed phenotype is stable for at least 4 weeks, providing a time window for rapid but also subchronic antidepressant treatment strategies. Furthermore, alterations in the development of a depressive-like state can be addressed using this approach. CDM, therefore, represents a useful tool to better understand depression and to develop novel treatment interventions.

Animal Models of Depression - Chronic Despair Model CDM

The chronic despair mouse model (CDM) of depression consists of repetitive forced swim sessions and another delayed swim phase as a read-out. It represents a suitable model for induction of a chronic depressive-like state stable for at least 4 weeks, amendable to evaluate subchronic and acute treatment interventions.

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. ...

Developing a Rat Model for Bipolar Disorder

Bipolar disorder is a mental health condition characterized by extreme mood swings, including periods of emotional highs (mania) and lows (depression). While the exact underlying neurobiology is not yet fully understood, imbalances in neurotransmitter systems, particularly dopamine, appear to play a central role. For this reason, manipulations of dopaminergic pathways have been used to model mania or depression in rodents. However, models that accurately represent the typical switch between these two episodes are rare, limiting face validity. In a unique model, modern techniques are used to temporarily increase dopamine D1 receptor expression, which has been implicated in the pathology of bipolar disorder. A tetracycline-inducible lentiviral construct that expresses the dopamine D1 receptor under the control of the calmodulin kinase II alpha promoter is stereotactically injected into the medial prefrontal cortex of adult rats. Dopamine D1 receptor overexpression is achieved by adding the tetracycline analog doxycycline to the animals&#39; drinking water, leading to an increase in reward-related, impulsive, and risk-taking behaviors and a decrease in anxiety. These behaviors resemble a mania-like phenotype. By removing doxycycline from the drinking water, a depressive-like phenotype, characterized by increased helplessness and anhedonia, can be induced within the same animal. This article provides a step-by-step protocol for performing the surgery, as well as procedures for inducing the bipolar disorder-like phenotype. Additionally, considerations for assessing behavioral changes associated with mania-like and depressive-like behavior are described. This promising model, which demonstrates good construct and face validity, offers a valuable tool for further investigating the pathophysiological mechanisms of bipolar disorder.

This article presents a protocol for the induction of a unique rat model of bipolar disorder that captures both mania-like and depressive-like behavior.

Bipolar disorder is a mental health condition characterized by extreme mood swings, including periods of emotional highs (mania) and lows (depression). ...

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

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