The authors would like to thank Thomas Grace for constructing Y-mazes, barriers, and social defeat cages. The authors would like to thank Jay Lee, Karina Stech, and Prachi Srivastava for assistance with data collection. This work was funded by NIMH Grant R01 MH112861 (BAS).

<ol>
	<li>Kessler, R. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lifetime+and+12-month+prevalence+of+DSM-III-R+psychiatric+disorders+in+the+United+States.+Results+from+the+National+Comorbidity+Survey.">Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey.</a> Arch Gen Psychiatry. 51 (1), 8-19 (1994).</li><li>Breslau, N., Davis, G. 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The authors have nothing to disclose.

While the chronic CORT paradigm provides a constant CORT dose in the drinking water, from experience there can be some variability in amount consumed by mice. Further, consumption can only be assessed for the total cage, and an average taken based on the number of mice in the cage. Additionally, spillage can occur when weighing the bottles, transferring the mice for behavior testing, or when changing to a fresh cage. However, tracking Vehicle and CORT consumption is still feasible and accurate across weeks of treatment a...

Mood disorders such as depression and anxiety are highly prevalent in today&#8217;s society. Decades of work has continuously searched for improved treatments and relevant rodent models to study these complex disorders1. Chronic stress is a contributing factor for mood disorders like depression2. Therefore, chronic stress paradigms such as chronic social defeat stress (SDS) and chronic corticosterone administration (CORT) were developed in male mice and are now widely used to assess the neurobiological and behavioral effects of chronic stress exposure. The most widely used behavioral tests for assessing chronic stress effects include tasks associated with avoidance behavior, such as elevated plus maze, open field, and novelty suppressed feeding, or with antidepressant efficacy, such as forced swim test. However, these behaviors in rodents arguably lack face and, more importantly, predictive validity and translational relevance for human disorders such as depression.
A popular chronic stress paradigm, chronic unpredictable mild stress (CUMS), has been validated extensively using behaviors such as sucrose preference3. CUMS reduces preference for a 1% sucrose solution compared to water and is historically interpreted as anhedonia-related behavior4,5. However, this reduction in sucrose preference is not observed in humans with major depressive disorder6,7. In addition, sucrose preference does not allow for the study of effortful reward motivation.
Recently, some research has shifted focus to other behaviors associated with motivation and reward8,9. These tasks have promising translational value because relatively similar behavior assessments can be conducted in both humans and rodents. Here, we describe the CORT and SDS paradigms and their effects in a Y-maze barrier behavioral task that measures motivation to exert effort for reward. We then discuss a new chronic stress paradigm that we developed, chronic non-discriminatory social defeat stress (CNSDS), which is effective in both male and female mice.
Chronic corticosterone administration (CORT) is a paradigm designed to mimic chronic stress without actual stress exposures. Activation of the hypothalamus-pituitary-adrenal axis by stress results in the endogenous release of the adrenal steroid cortisol in humans10,11,12 and corticosterone in mice13,14. Delivery of corticosterone through the drinking water of adult male mice for at least 4 weeks results in maladaptive behavioral responses in avoidance tasks such as open field, elevated plus maze, and novelty suppressed feeding10,11,12,13,14,15,16. Interestingly, CORT also affects reward processing in instrumental tasks16,17,18,19. The CORT paradigm described here produces a consistent serum concentration of below 100 ng/mL CORT, which is more than five times less than that produced by an acute stressor such as forced swim15. Therefore, chronic CORT administration is unlikely to cause hypercortisolemia. While chronic CORT is only effective in male mice20, we recently demonstrated that it produces a robust shift in effortful responding in the Y-maze barrier task21. To our knowledge, this was one of the first studies to examine the effects of chronic stress on an effort-related choice behavior in male mice21. One previous study first demonstrated the impact of acute restraint stress on effort-based decision making in rats22. In effort-related choice behaviors, an animal chooses to either exert effort for a high-value reward or accept a lower-value reward that is more freely available. In humans, the effort-expenditure for rewards task (EEfRT), is a computer game developed to be analogous to effort-related choice tasks in mice23. Depression results in maladaptive responses in EEfRT (decreased likelihood of choosing hard tasks for high-value rewards). Therefore, effort-related choice tasks in rodents are particularly interesting because of their translational relevance.
Chronic social defeat stress (SDS) is one of the more widely used preclinical stress models in male mice. It is a 10-day protocol where large, aggressive retired breeder CD-1 males attack experimental mice, typically C57BL/6J, in 5 min daily sessions24. This produces a robust maladaptive behavioral phenotype in a subset of experimental mice. A social interaction test is used to stratify mice into resilient or susceptible populations to the defeat stress, and several studies have used this unique characteristic of SDS to probe the molecular and neural circuit mechanisms underlying stress reliance and susceptibility. Here we describe the details of the CORT paradigm and its implementation for the Y-maze barrier behavioral task. We also discuss SDS effects in the Y-maze barrier task. The Y-maze barrier task is based on the T-maze barrier task, which is used primarily in rats to measure motivation to expend effort for high or low rewards present in the two arms of the maze8,9,25. This task has also been implemented to study effortful responding in mice administered caffeine or dopamine antagonists in mice26. Rodents can either expend greater effort by climbing barriers of progressively increasing height in one arm of the maze for a higher reward value, typically 4 reward pellets, or expend significantly less effort in the other arm of the maze to receive only 2 reward pellets9. 10-day social defeat paradigms produce a robust maladaptive phenotype in susceptible mice that lasts approximately 30 days, so we modified the Y-maze barrier task to more rapidly train and test animals in order to complete all experiments within this 30-day timeframe24. Therefore, here we also detail a Y-maze barrier behavioral task protocol containing condensed training sessions and single barrier test sessions to measure motivation to expend effort for reward in chronic stress-exposed mice.
Unfortunately, both chronic corticosterone and chronic social defeat stress were developed in male mice and are less effective in female mice. This is highly problematic as women are more likely than men to be diagnosed with mood disorders such as depression1. Clever adaptations to SDS have allowed usage in female mice but require difficult surgeries or tedious urine collection26,27. We recently described a simple modification to the SDS paradigm, called chronic non-discriminatory social defeat stress (CNSDS). CNSDS allows susceptible and resilient stratification of both experimental male and female mice28. Both female and male susceptible mice exposed to CNSDS show increased avoidance of open arms in elevated-plus maze and of the center in open field and display increased latency to eat in novelty-suppressed feeding. CNSDS also is more efficient than other modifications to SDS, as both sexes are combined in defeat sessions. This results in an increased yield of experimental mice without an associated increase in time and effort required to complete the protocol. Therefore, we conclude this manuscript with an in-depth presentation of this recently developed chronic stress paradigm.

<table>
	<tbody>
		<tr>
			<td>Acrylic Sheet</td>
			<td>McMaster Carr</td>
			<td>8560K215</td>
			<td>Clear, 3/16&#34; thick, 24&#34; X 36&#34;</td>
		</tr>
		<tr>
			<td>Beta-cyclodextrin</td>
			<td>Sigma-Aldrich</td>
			<td>C4767</td>
			<td>500 mg</td>
		</tr>
		<tr>
			<td>C57BL/6J Mice</td>
			<td>Jackson Labs</td>
			<td>000664</td>
			<td>Adults age 7-8 weeks</td>
		</tr>
		<tr>
			<td>Corticosterone</td>
			<td>Sigma-Aldrich</td>
			<td>C2505 or C27840</td>
			<td>100 or 500 mg</td>
		</tr>
		<tr>
			<td>Male CD-1 Mice</td>
			<td>Charles River</td>
			<td>022</td>
			<td>&#34;Retired Breeders&#34;</td>
		</tr>
		<tr>
			<td>PVC Acrylic Sheet</td>
			<td>McMaster Carr</td>
			<td>8560K215</td>
			<td>White, 3/16&#34; thick, 48&#34; X 48&#34;</td>
		</tr>
		<tr>
			<td>Solidstate Ultrasonic Cleaner</td>
			<td>Fisher Scientific</td>
			<td>FS-28</td>
			<td>Must reach 40 kHz</td>
		</tr>
		<tr>
			<td>Steel Wire Cloth</td>
			<td>McMaster Carr</td>
			<td>9219T143</td>
			<td>1 ft X 2 ft</td>
		</tr>
	</tbody>
</table>

chronic stress shifts effort-related choice behavior in a y-maze barrier task in mice

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that measures motivation to expend effort and obtain reward. In mice, chronic stress exposure significantly impacts motivation to work for a higher value reward when a lesser value reward is freely available compared to unstressed mice. Here we describe the chronic corticosterone administration paradigm, which produces a shift in effortful responding in the Y-maze barrier task. In the Y-maze task, one arm contains 4 food pellets, while the other arm contains only 2 pellets. After mice learn to select the high reward arm, barriers with progressively increasing height are then introduced into the high reward arm over multiple test sessions. Unfortunately, most chronic stress paradigms (including corticosterone and social defeat) were developed in male mice and are less effective in female mice. Therefore, we also discuss chronic non-discriminatory social defeat stress (CNSDS), a stress paradigm we developed that is effective in both male and female mice. Repeating results with multiple distinct chronic stressors in male and female mice combined with increased usage of translationally relevant behavior tasks will help to advance the understanding of how chronic stress can precipitate mood disorders.

Chronic CORT was administered for 4 weeks followed by Y-maze barrier training and testing (Figure 1A). In a separate cohort, the 10-day SDS paradigm was similarly followed by training and testing in the Y-maze barrier task (Figure 1C), to determine the effect of these chronic stress paradigms on effort-related choice behavior in male mice. Chronic CORT and SDS both reduced mean body weight compared to Vehicle mice and SDS Control mice as determined by t...

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Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice

The Y-maze barrier task is a behavior test that examines motivation to expend effort for reward. Here, we discuss testing multiple well-validated chronic stressors including chronic corticosterone and social defeat stress with this behavior, as well as the novel chronic non-discriminatory social defeat stress (CNSDS), which is effective in females.

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that ...

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10.9K Views.  The State University of New Jersey. The Y-maze barrier task is a behavior test that examines motivation to expend effort for reward. Here, we discuss testing multiple well-validated chronic stressors including chronic corticosterone and social defeat stress with this behavior, as well as the novel chronic non-discriminatory social defeat stress (CNSDS), which is effective in females.

Video: Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.

This article describes the use of chronic resident intruder social stress as an ethologically relevant paradigm to model postpartum depression and anxiety in lactating rodents.

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals ...

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, modifications to the standard task, can be used to systematically tax the neural systems controlling either attention or impulse control. Importantly, these challenges have consistent effects on behavior across laboratories in intact animals and can reveal either enhancements or deficits in cognitive function that are not apparent when rats are only tested on the standard task. The variety of behavioral measures that are collected can be used to determine if other factors (i.e., sedation, motivation deficits, locomotor impairments) are contributing to changes in performance. The versatility of the 5CSRTT is further enhanced because it is amenable to combination with pharmacological, molecular, and genetic techniques.

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, which are modifications of the standard task, increase flexibility of the task and can be combined with other manipulations to more fully characterize behavior.

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. ...

Determining Ultrasonic Vocalization Preferences in Mice using a Two-choice Playback Test

Mice emit ultrasonic vocalizations (USVs) during a variety of conditions, such as pup isolation and adult social interactions. These USVs differ with age, sex, condition, and genetic background of the emitting animal. Although many studies have characterized these differences, whether receiver mice can discriminate among objectively different USVs and show preferences for particular sound traits remains to be elucidated. To determine whether mice can discriminate between different characteristics of USVs, a playback experiment was developed recently, in which preference responses of mice to two different USVs could be evaluated in the form of a place preference.
First, USVs from mice were recorded. Then, the recorded USVs were edited, trimmed accordingly, and exported as stereophonic sound files. Next, the USV amplitudes generated by the two ultrasound emitters used in the experiment were adjusted to the same sound pressure level. Nanocrystalline silicon thermo-acoustic emitters were used to play the USVs back. Finally, to investigate the preference of subject mice to selected USVs, pairs of two differing USV signals were played back simultaneously in a two-choice test box. By repeatedly entering a defined zone near an ultrasound emitter and searching the wire mesh in front of the emitter, the mouse reveals its preference for one sound over another. This model allows comparing the attractiveness of the various features of mouse USVs, in various contexts.

Ultrasonic vocalizations (USVs) in mice differ depending on age, sex, condition, and genetic background. Using two ultrasound emitters broadcasting simultaneously in different locations, this two-choice test can evaluate murine recognition and preference responses to different characteristics of USVs.

Mice emit ultrasonic vocalizations (USVs) during a variety of conditions, such as pup isolation and adult social interactions. These USVs differ with age, ...

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)&#8212;a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks.

Previous research on the social dimension of stress has focused on two important variables: social identity and social support. This protocol introduces an effective experimental manipulation of these two social variables and describes their implementation in a standard stress induction paradigm (Trier Social Stress Test).

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations ...

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 ...

A Two-interval Forced-choice Task for Multisensory Comparisons

We provide a procedure for a psychophysics experiment in humans based on a previously described paradigm aimed to characterize the perceptual duration of intervals within the range of milliseconds of visual, acoustic, and audiovisual aperiodic trains of six pulses. In this task, each of the trials consists of two consecutive intramodal intervals where the participants press the upward arrow key to report that the second stimulus lasted longer than the reference, or the downward arrow key to indicate otherwise. The analysis of the behavior results in psychometric functions of the probability of estimating the comparison stimulus to be longer than the reference, as a function of the comparison intervals. In conclusion, we advance a way of implementing standard programming software to create visual, acoustic, and audiovisual stimuli, and to generate a two-interval forced-choice (2IFC) task by delivering stimuli through noise-blocking headphones and a computer&#39;s monitor.

Psychophysics is essential for studying perception phenomena through sensory information. Here we present a protocol to perform a two-interval forced-choice task as implemented in a previous report on human psychophysics where participants estimated the duration of visual, auditory, or audiovisual intervals of aperiodic trains of pulses.

We provide a procedure for a psychophysics experiment in humans based on a previously described paradigm aimed to characterize the perceptual duration of ...

Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various physiological or pathological changes. The object location task (OLT) and the novel object recognition task (NORT) are two effective behavioral tasks commonly used to reveal the function and relative health of specific brain regions involved in memory. While both of these tests exploit the inherent preference of mice for the novelty to reveal memory for previously encountered objects, the OLT primarily evaluates spatial learning, which relies heavily on hippocampal activity. The NORT, in contrast, evaluates non-spatial learning of object identity, which relies on multiple brain regions. Both tasks require an open-field-testing arena, objects with equivalent intrinsic value to mice, appropriate environmental cues, and video recording equipment and the software. Commercially available systems, while convenient, can be costly. This manuscript details a simple, cost-effective method for building the arenas and setting up the equipment necessary to perform the OLT and NORT. Furthermore, the manuscript describes an efficient testing protocol that incorporates both OLT and NORT and provides typical methods for data acquisition and analysis, as well as representative results. Successful completion of these tests can provide valuable insight into the memory function of various mouse model systems and appraise the underlying neural regions that support these functions.

Here we provide a protocol which includes comprehensive instructions for the economical establishment of murine object location and novel object recognition behavioral testing, including the design, cost, and construction of required equipment as well as execution of behavioral testing, data collection, and analysis.

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various ...

Integrating Visual Psychophysical Assays within a Y-Maze to Isolate the Role that Visual Features Play in Navigational Decisions

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired investigations into collective motion, specifically, their ability to integrate environmental and social information across ecological contexts. This demonstration illustrates techniques used for quantifying behavioral responses of fish, in this case, Golden Shiner (Notemigonus crysoleucas), to visual stimuli using computer visualization and digital image analysis. Recent advancements in computer visualization allow for empirical testing in the lab where visual features can be controlled and finely manipulated to isolate the mechanisms of social interactions. The purpose of this method is to isolate visual features that can influence the directional decisions of the individual, whether solitary or with groups. This protocol provides specifics on the physical Y-maze domain, recording equipment, settings and calibrations of the projector and animation, experimental steps and data analyses. These techniques demonstrate that computer animation can elicit biologically-meaningful responses. Moreover, the techniques are easily adaptable to test alternative hypotheses, domains, and species for a broad range of experimental applications. The use of virtual stimuli allows for the reduction and replacement of the number of live animals required, and consequently reduces laboratory overhead.
This demonstration tests the hypothesis that small relative differences in the movement speeds (2 body lengths per second) of virtual conspecifics will improve the speed and accuracy with which shiners follow the directional cues provided by the virtual silhouettes. Results show that shiners directional decisions are significantly affected by increases in the speed of the visual cues, even in the presence of background noise (67% image coherency). In the absence of any motion cues, subjects chose their directions at random. The relationship between decision speed and cue speed was variable and increases in cue speed had a modestly disproportionate influence on directional accuracy.

Here, we present a protocol to demonstrate a behavioral assay that quantifies how alternative visual features, such as motion cues, influence directional decisions in fish. Representative data are presented on the speed and accuracy where Golden Shiner (Notemigonus crysoleucas) follow virtual fish movements.

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired ...

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, ...