I appreciate the editorial feedback provided by Holly Rahurahu and Sam Shaffer.

The experiments and protocols have been approved by the Institutional Animal Care and Use Committee (IACUC) at the University of North Carolina at Chapel Hill (mice) and Fairfield University (rats) and follow the guidelines of NIH10.
1. Restraint stress in mice
NOTE: Mice offer a number of advantages when studying the effects of stress on physiology and neuronal systems. With the prevalence of transgenic mouse lines, mechanistic investigations into the interactions between genes and stress exposures are readily feasible. Whether using transgenic or wild-type mice, consideration of the background strain is recommended. Additionally, due to their size and social housing, mice offer an advantage in space utilization over other species.
<ol>
	<li>Restraint stress exposure
	<ol>
		<li>Randomly assign mice to homecage control, acute restraint stress, or chronic restraint stress groups.</li>
		<li>Determine the length of stress exposure. For acute stressors, use a single session lasting 5 min up to 12 h confined in the restraint apparatus. For chronic stressors, ensure that the session matches the length of the acute stressor but is repeated daily for as short as 3 days and as long as 21 days. 
		NOTE: Because mice will be without access to food and water while in the restraint conditions, consider whether homecage control animals should also lack access to food and water.</li>
		<li>Modify 50 mL conical tubes to add ventilation holes.
		<ol>
			<li>Use a power drill with a 1/8&#34; bit to evenly space holes around each conical tube to ensure airflow throughout all areas of the tube.</li>
			<li>Place these holes to allow the mouse access to air regardless of which direction the mouse is facing in the tube. Ensure no sharp edges remain after modification. 
			NOTE: These modified conical tubes should be effective for most adult mice (~20-40 g) but may not restrain small/young mice or larger strains.</li>
		</ol>
		</li>
		<li>In a testing room, separate from animal housing and behavioral testing, place the restraint-assigned animal into the modified conical tube with the cap attached to confine the mouse in the tube for the designated length of restraint. 
		NOTE: The specifics of the testing room design can vary based on the space available in the facility; the room could include fume hoods and other laboratory equipment and/or laboratory tables/benches or be an empty procedure room. However, regardless of the room setup, the restraint room environment should remain consistent over repeated restraint exposures to avoid context-induced alterations in stress responses11.</li>
		<li>Place the restraint tube horizontally on a flat surface. If needed, secure the tube with laboratory tape or a pipette basin/reagent reservoir so it does not roll with the mouse inside. 
		NOTE: Under stress conditions, mice produce ultrasonic vocalizations. Consider whether the study design requires sound isolation from other restrained subjects12. Corticosterone and other markers of stress responses follow circadian rhythms. As such, considerations regarding the lighting conditions and time of stressor should be made. Across stress groups, restraint should occur at a consistent time of day, preferably early in the light cycle13,14,15. For the study presented here, mice were restrained for approximately 3 h following lights on.</li>
		<li>Monitor each animal during restraint stress at least every 20 min. Visually determine whether the animal is displaying unusual responses (slow breathing, lack of movement). If observed, remove the mouse from the restraint tube, contact a veterinarian, and exclude the mouse from the study.</li>
		<li>Return the mouse to the home cage and provide access to food and water.</li>
	</ol>
	</li>
</ol>
2. Restraint stress in rats
NOTE: As larger rodents, rats have advantages to consider when investigating the effects of stress. Like mice, rats have various strains with differential responses to stress exposure16,17. Additionally, the increased size of rats makes rats easier to use with certain behavioral measures, e.g., drug self-administration.
<ol>
	<li>Restraint stress exposure
	<ol>
		<li>Randomly assign the rat to homecage control, acute restraint stress, or chronic restraint stress groups.</li>
		<li>Determine the length of stress exposure. For acute stressors, use a single session lasting 5 min up to 12 h confined in the restraint apparatus. For chronic stressors, ensure that the session matches the length of the acute stressor but is repeated daily for as short as 3 days and as long as 21 days. 
		NOTE: Because rats will be without access to food and water while in the restraint condition, consider whether homecage control animals should also lack access to food and water.</li>
		<li>For a commercially available restraint tube, follow the steps described below. 
		NOTE: Commercially available restraint tubes for rats are available. These devices have a variety of designs, including metal wire, containers, and plastic/plexiglass tubes with rounded and flat-bottom options. Each option is simple to use.
		<ol>
			<li>Insert the rat into the device, then add a plug adjusted to the subject&#39;s size, and lock it in place. When placed in the restraint tube, ensure that the rat is snugly confined to prevent head-to-tail turns but can breathe easily. 
			NOTE: These devices are designed for restraining rats and do not need modification for respiration. This study uses the tailveiner restrainer (Table of Materials), which includes suction cups on a platform under the tube to secure the device. An additional benefit of this device is that the tail is accessible outside of the device for control of the subject during insertion and removal from the tube or tail vein blood draw during restraint.</li>
		</ol>
		</li>
		<li>In a testing room separate from animal housing and behavioral testing, place restraint-assigned animas into the restraint tube for the designated length of restraint. Place the restraint tube horizontally on a flat surface. 
		NOTE: Under stress conditions, rats also produce ultrasonic vocalizations. Consider whether the study design requires sound isolation from other restrained subjects.</li>
		<li>Monitor each animal during restraint stress at least every 20 min. Visually determine whether the animal is displaying unusual responses (slow breathing, lack of movement). If observed, remove the rat from the restraint tube, contact a veterinarian, and exclude the rat from the study.</li>
		<li>Return the rat to the home cage and provide access to food and water.</li>
	</ol>
	</li>
</ol>
3. Assessments of stress
<ol>
	<li>Measurement of HPA activation
	<ol>
		<li>If appropriate, following restraint stress exposure or removal from homecage, rapidly decapitate subjects to collect trunk blood into heparinized tubes.</li>
		<li>Isolate plasma via centrifugation and store plasma samples at -80 &#176;C. Analyze blood corticosterone using an enzyme-linked immunosorbent assay (ELISA) kit. 
		NOTE: Although corticosterone is often used as a readout of the severity of stress exposure, especially acute stress, corticosterone levels do not always correlate with stress-induced behavioral changes6. Furthermore, the HPA axis response regulating corticosterone release habituates with repeated exposure to the same stressor18. Alternatively, adrenocorticotrophic hormone (ACTH) may be a more reliable measure of the intensity of an acute stressor4. It remains elevated for approximately an hour following the cessation of stressor exposure, but severe and prolonged (approximately &#62; 2 h) stress may fatigue its production.</li>
	</ol>
	</li>
	<li>Behavioral effects
	<ol>
		<li>If appropriate, following restraint stress exposure or removal from homecage, assess the behavioral performance of the rodent with the appropriate behavioral task. 
		&#8203;NOTE: Further information regarding the effects of restraint on various behavioral models can be found in the discussion section.</li>
	</ol>
	</li>
	<li>Neurobiology
	<ol>
		<li>Alternatively or additionally, assess neurobiological function following restraint stress exposure or control. A wide range of assays can investigate restraint stress effects on cellular, synaptic, and circuitry. Depending on the assay, implant an&#160;in vivo&#160;measurement device or harvest brain tissue to perform the selected analysis. 
		NOTE: The effects of stress on cell-type specific changes in protein synthesis and epigenetic modifications have been thoroughly reviewed by McEwen and colleagues1. These genetic and protein modifications induce plasticity to alter synaptic connections and circuitry. In order to conduct these studies, harvest brain tissue following stress exposure and perform genomic, proteomic, ex vivo physiology, and other analyses. Alternatively, assess neurobiological changes through in vivo measurements such as microdialysis, fast-scan cyclic voltammetry (FSCV), fiber photometry, and others. These approaches record neurochemical release and neuronal activation, both following restraint stress exposure2,19&#160;and now during restraint8,9,20. The toolbox to assess the neurobiological mechanisms underlying the effects of restraint stress is rapidly expanding allowing new insights into the complexities of stress.</li>
	</ol>
	</li>
</ol>

Impact of Restraint Stress on Physiology and Neurobiology in Rodent Models

No conflicts of interest to report.

To investigate the effects of stress on physiological, neurobiological, and behavioral functions in rodent models, conditions that produce stress for rodents must be used. Among these considerations are the conditions that produce stress responses in the subject. Restraint is a validated procedure to produce physiological and behavioral responses in rodents matching stress effects in humans. Using a methodology similar to this protocol, restraint has been used to assess a number of molecu...

Due to the universal experience of stress, investigations into the mechanisms of altered responses following stress exposures have been a consistent area of research for several decades1. These investigations have begun to parse out aspects of stress that may be beneficial to increase adaptability and responsiveness to acute stressors from stress experiences that induce maladaptive alterations of physiological and behavioral functions, often resulting from prolonged exposure to repeated and/or unpredictable stressors. Many of these responses to stressors impact the brain function, the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic and parasympathetic branches of the autonomic nervous system, and the immune system. Exposure to stressors initiates the increased release of corticotropin-releasing factor (CRF) to increase adrenocorticotropic hormone (ACTH) and glucocorticoid hormones, such as cortisol in primates and many other mammals and corticosterone in rodents2. Additionally, epinephrine and norepinephrine are released throughout the periphery and brain as part of the sympathetic nervous system response3. These chemical signals then interact with a number of physiological systems, such as immune function, metabolism, reproduction, and neuronal reactivity4.
Stressful experiences are associated with a myriad of conditions, including increases in anxiety and depression, alterations in learning and memory, impairments in decision-making and executive function, and susceptibility to substance use disorder, among others. Each of these effects is dependent on both parameters of the stressor and the characteristics of the individual experiencing stress4. The nature of the stressor, as acute or chronic and as controllable or unpredictable, substantially alters the outcomes observed. These aspects of stress appear consistent between human experiences and animal models. Thus, to model stress in animal studies, careful consideration must be used to select parameters of stress exposure that are appropriate for the species, sex, and condition.
Although a number of stressors are available for studies with rodents (including psychosocial stressors like social isolation stress or social defeat, pharmacological stressors like cortisol or yohimbine administration, physical stressors like footshock and restraint, and multimodal stressors that combine or alternate between conditions), the focus of this manuscript will be on the use of restraint stress in mice and rats. Restraint stress might be chosen over other stressors because it is easy to perform, inexpensive, adjustable to various sizes of rodents, scalable to both acute and long-term periods, and rarely results in adverse harm to the subject5. Although this manuscript focuses on the lasting changes induced by restraint stress exposure, some studies use restraint in rodents to examine mechanisms and behaviors that occur during restraint, including active coping behaviors involved in escaping the stressor6,7,8,9. The goal of this manuscript is to provide methodological considerations to assess the impact of restraint stress on mice or rat subjects.

<table><tbody><tr><td>50 mL General Purpose Screwcap Conical Tube</td><td>Globe Scientific</td><td>6288</td><td></td></tr><tr><td>Disposable Pipette Basin</td><td>Fisher Scientific</td><td>13-681-500</td><td></td></tr><tr><td>ELISA Kit for Corticosterone</td><td>Arbor Assays</td><td>K014-H</td><td></td></tr><tr><td>Tailveiner Restrainer Tube</td><td>Braintree Scientific</td><td>RTV</td><td></td></tr></tbody></table>

restraint to induce stress in mice and rats

Across all animal species, exposure to stressful conditions induces stress responses. One method to study the effects of stress using rodent models is the restraint stress procedure. Restraint stress has been used for decades to investigate changes in physiology, genetics, neurobiology, immunology, and other systems impacted by stress. Due to the ease of performing the procedure, low cost, and numerous modifications to scale for the intensity and duration of stress exposure, a vast literature of studies has used restraint stress in mice and rats. As one example, this study presents previously published data showing the impact of restraint stress in transgenic mice on plasma corticosterone levels and optogenetically-induced norepinephrine release. Acute restraint stress increased plasma corticosterone levels, yet this effect was blunted in mice following repeat restraint stress. However, stimulated norepinephrine release in the bed nucleus of the stria terminalis was increased only in the repeat restraint stress group. These data highlight important considerations of restraint parameters on dependent measures. Additional descriptions of restraint stress in rats are also included for comparison. Finally, the influence of the parameters of the restraint (e.g., acute vs. chronic) and characteristics of the animal subjects (strain, sex, age) are discussed.

In a previously published study21, the restraint stress procedures described in this manuscript were used to assess the impact of restraint stress on the regulation of cortisol and norepinephrine, falling under the broad possibilities of changes in neurobiology induced by stress mentioned in protocol 3.3. In this study, we utilized the protocol described above for the restraint of mice. Additional details that are beyond the scope of the restraint focus of this article, e.g., the rationale for bra...

Restraint to Induce Stress in Mice and Rats

This article covers the procedures to induce stress responses using physical restraint stress in mice and rats. Additional considerations that should be observed when selecting and using restraint stress in rodent models are discussed.

Across all animal species, exposure to stressful conditions induces stress responses. One method to study the effects of stress using rodent models is the ...

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1.0K Views.  Fairfield University. Mijn onderzoek richt zich op de neurobiologische mechanismen die van invloed zijn op stresseffecten, de gedragseffecten van drugsmisbruik en de kruising tussen beide. Kortom, mijn laboratorium probeert te beantwoorden hoe stresservaringen bijdragen aan stoornissen in het gebruik van middelen en hoe we interventies kunnen ontwikkelen om deze relatie aan te pakken. Mijn onderzoek heeft aangetoond dat blootstelling aan stress noradrenerge systemen verandert op e...

Video: Terughoudendheid om stress op te wekken bij muizen en ratten

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 ...

Behavior

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, ...

Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented. Described here is an adaptation of an automated operant strategy shifting paradigm to assess how variations in stress affect cognitive flexibility in male and female Sprague Dawley rats. Specifically, restraint stress is used before or after training in this operant-based task to examine how stress affects cognitive performance in both sexes. Particular brain areas associated with each task in this automated paradigm have been well-established (i.e., the medial prefrontal cortex and orbitofrontal cortex). This allows for targeted manipulations during the experiment or the assessment of particular genes and proteins in these regions upon completion of the paradigm. This paradigm also allows for the detection of different types of performance errors that occur after stress, each of which has defined neural substrates. Also identified are distinct sex differences in perseverative errors after a repeated restraint stress paradigm. The use of these techniques in a preclinical model may reveal how stress affects the brain and impairs cognition in psychiatric disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), which display marked sex differences in prevalence.

Stressful life events impair cognitive function, increasing the risk of psychiatric disorders. This protocol illustrates how stress affects cognitive flexibility using an automated operant strategy shifting paradigm in male and female Sprague Dawley rats. Specific brain areas underlying particular behaviors are discussed, and translational relevance of results are explored.

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and ...

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.

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 ...

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants

The peripartum period is considered a sensitive period where adverse maternal exposures can result in long-term negative consequences for both mother and offspring, including the development of neuropsychiatric disorders. Risk factors linked to the emergence of affective dysregulation in the maternal-infant dyad have been extensively studied. Exposure to psychosocial stress during pregnancy has consistently emerged as one of the strongest predictors. Several rodent models have been created to explore this association; however, these models rely on the use of physical stressors or a limited number of psychosocial stressors presented in a repetitive fashion, which do not accurately capture the type, intensity, and frequency of stressors experienced by women. To overcome these limitations, a chronic psychosocial stress (CGS) paradigm was generated that employs various psychosocial insults of different intensity presented in an unpredictable fashion. The manuscript describes this novel CGS paradigm where pregnant female mice, from gestational day 6.5 to 17.5, are exposed to various stressors during the day and overnight. Day stressors, two per day separated by a 2 h break, range from exposure to foreign objects or predator odor to frequent changes in bedding, removal of bedding, and cage tilting. Overnight stressors include continuous light exposure, changing cage mates, or wetting bedding. We have previously shown that exposure to CGS results in the development of maternal neuroendocrine and behavioral abnormalities, including increased stress reactivity, the emergence of fragmented maternal care patterns, anhedonia, and anxiety-related behaviors, core features of women suffering from perinatal mood and anxiety disorders. This CGS model, therefore, becomes a unique tool that can be used to elucidate molecular defects underlying maternal affective dysregulation, as well as trans-placental mechanisms that impact fetal neurodevelopment and result in negative long-term behavioral consequences in the offspring.

The chronic psychosocial stress (CGS) paradigm employs clinically relevant stressors during pregnancy in mice to model psychiatric disorders of mothers and infants. Here, we provide a step-by-step procedure of applying the CGS paradigm and downstream assessments to validate this model.

The peripartum period is considered a sensitive period where adverse maternal exposures can result in long-term negative consequences for both mother and ...

Handling Techniques to Reduce Stress in Mice

Laboratory animals are subjected to multiple manipulations by scientists or animal care providers. The stress this causes can have profound effects on&#160;animal well-being and can also be a confounding factor for experimental variables such as anxiety measures. Over the years, handling techniques that minimize handling-related stress have been developed with a particular focus on rats, and little attention to mice. However, it has been shown that mice can be habituated to manipulations using handling techniques. Habituating mice to handling reduces stress, facilitates routine handling, improves animal wellbeing, decreases data variability, and improves experimental reliability. Despite beneficial effects of handling, the tail-pick up approach, which is particularly stressful, is still widely used. This paper provides a detailed description and demonstration of a newly developed mouse-handling technique intended to minimize the stress experienced by the animal during human interaction. This manual technique is performed over 3 days (3D-handling technique) and focuses on the animal&#39;s capacity to habituate to the experimenter. This study also shows the effect of previously established tunnel handling techniques (using a polycarbonate tunnel) and the tail-pick up technique. Specifically studied are their effects on anxiety-like behaviors, using behavioral tests (Elevated-Plus Maze and Novelty Suppressed Feeding), voluntary interaction with experimenters and physiological measurement (corticosterone levels). The 3D-handling technique and the tunnel handling technique reduced anxiety-like phenotypes. In the first experiment, using 6-month-old male mice, the 3D-handling technique significantly improved experimenter interaction. In the second experiment, using 2.5-month-old female, it reduced corticosterone levels. As such, the 3D-handling is a useful approach in scenarios where interaction with the experimenter is required or preferred, or where tunnel handling may not be possible during the experiment.

This paper describes a handling technique in mice, the 3D-handling technique, which facilitates routine handling by reducing anxiety-like behaviors and presents details on two existing related techniques (tunnel and tail handling).

Laboratory animals are subjected to multiple manipulations by scientists or animal care providers. The stress this causes can have profound effects ...

Threat-Safety Test for Stress Susceptibility or Resilience in Mice Models

Social Threat-Safety Test Uncovers Psychosocial Stress-Related Phenotypes

Social stress is a major cause of the development of mental disorders. To enhance the translational value of preclinical studies, social stress experience and its behavioral impact on mice should be comparable to humans. Chronic social defeat (CSD) utilizes a type of social stress involving physical attacks and sensory threats to induce mental dysfunctions resembling human affective disorders. To strengthen the psychosocial component of CSD, a 10-day CSD protocol was applied in which daily physical attacks are standardized to three 10 s episodes followed by a 24 h sensory phase. After the 10th sensory phase, the CSD protocol is followed by a refined behavioral assay called the social threat-safety test (STST). Post-stress behavioral assays need to determine how and to what extent the social stressor has influenced behavior. The STST allows chronically socially defeated male mice to interact with 2 novel male individuals (social targets): one social target from the attacking strain encountered during the CSD days and the other from a novel strain. Both are presented simultaneously in different compartments of a three-chambered test arena. The test enables a simultaneous assessment of social avoidance development to measure successful aversive conditioned learning and social threat-safety discrimination ability. The development of social avoidance towards both strains reflects a generalized aversive response and thus, a measurement of stress susceptibility. Meanwhile, the development of social avoidance towards only the attacking strain reflects threat-safety discrimination and thus, a measurement of stress resilience. Finally, the absence of social avoidance towards the attacking strain reflects impaired aversive conditioned learning. The protocol aims to refine the currently used mouse models of stress susceptibility/resilience by including translational criteria, specifically threat-safety discrimination and aversive response generalization, to categorize a single group of chronically socially defeated animals into resilient and susceptible subgroups, eventually advancing future translational approaches.

Author Spotlight: Unveiling Mechanisms of Stress Resilience - Significant Findings, Advancements, and Future Research

The social threat-safety test allows a simultaneous assessment of social avoidance development as a measurement of aversive conditioned learning and social threat-safety discrimination ability, both utilized to identify stress-susceptible and stress-resilient individuals within a single group of chronically socially defeated male mice.

Social stress is a major cause of the development of mental disorders. To enhance the translational value of preclinical studies, social stress experience ...

Manual Restraint and Common Compound Administration Routes in Mice and Rats

Being able to safely and effectively restrain mice and rats is an important part of conducting research. Working confidently and humanely with mice and rats requires a basic competency in handling and restraint methods. This article will present the basic principles required to safely handle animals. One-handed, two-handed, and restraint with specially designed restraint objects will be illustrated. Often, another part of the research or testing use of animals is the effective administration of compounds to mice and rats. Although there are a large number of possible administration routes (limited only by the size and organs of the animal), most are not used regularly in research. This video will illustrate several of the more common routes, including intravenous, intramuscular, subcutaneous, and oral gavage. The goal of this article is to expose a viewer unfamiliar with these techniques to basic restraint and substance administration routes. This video does not replace required hands-on training at your facility, but is meant to augment and supplement that training.

Working safely and humanely with research rodents requires a core competency in handling and restraint methods. This article will present the basic principles required to safely handle and effectively administer compounds to mice and rats.

Being able to safely and effectively restrain mice and rats is an important part of conducting research.  Working confidently and humanely with mice and ...

Biology

Rodent Handling and Restraint Techniques

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN&#160;
It has been demonstrated that even minimal handling of mice and rats is stressful to the animals. Handling for cage changing and other noninvasive procedures causes an increase in heart rate, blood pressure, and other physiological parameters, such as serum corticosterone levels. Fluctuations can continue for up to several hours. The methods of restraint required for injections and blood withdrawals also cause physiological changes that can potentially affect scientific data. Training in the proper handling of mice and rats is required to minimize the effects to the animals.1 Mice and rats can be restrained manually with restraint devices, or with chemical agents. Manual methods and the use of restraint devices are covered in this manuscript. All restraint methods include the process of lifting the animals from their home cage.

Proper Handling and Restraining Techniques of Rodents

Source: Kay Stewart, RVT, RLATG, CMAR; Valerie A. Schroeder, RVT, RLATG. University of Notre Dame, IN&#160;
It has been demonstrated that even minimal ...

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Inducing Depression-like Behavior in a Mouse via Immobilization Stress

Source: Son, H., et al., <a href="https://app.jove.com/v/59546">A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice.</a> J. Vis. Exp. (2019).
This video demonstrates the method of inducing chronic stress in a mouse through repeated immobilization, leading to corticosterone release and reduced glutamate receptor activity in neurons, which results in depression-like behavior.

Restraint to Induce Stress in Mice and Rats

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