Name: the forced swim test as a model of depressive-like behavior
Uploaded: 2015-03-02T15:00:00
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

BEMÆRK: Alle forsøgsprotokoller blev godkendt af Den Internationale Komité for Animal Care og brug i Israel. Blev gjort alt for at minimere antallet af anvendte dyr og deres lidelser. 1. Forberedelse af Forced Swim Test <ol><li> Brug to tilstødende værelser. Brug en plads som en &quot;venteværelse&quot; til at holde dyr før adfærdsmæssige test, og den anden til at udføre proceduren. </li><li> Forbered transparente cylindriske glasbeholdere (den eneste begrænsning for antallet af...

FST bruges til at overvåge depressive-lignende adfærd og er baseret på den antagelse, at immobilitet afspejler et mål for adfærdsmæssig fortvivlelse 3. De væsentligste fordele ved denne fremgangsmåde ligger i den relativt nem betjening og hurtige resultater. Desuden dens følsomhed over for en bred vifte af antidepressive lægemidler, der gør det til et egnet screening test er en af de vigtigste funktioner, der fører til den høje prædiktive gyldighed 29. Vigtigt er det, kan denne test o...

Depression er en livstruende psykiatrisk lidelse og et stort folkesundhedsproblem i hele verden med en incidens på 5% og en levetid på 15-20%. Desuden skønnes det, at i 2020 depression vil være i top tre bidragydere til sygdomsbyrden 1,2. Depression er forbundet med handicap, nedsat livskvalitet, øget sundhedsrelaterede omkostninger og betragtes som en vigtigste risikofaktor for mange sygdomme, herunder hjerte-kar, metaboliske og neuropsykiatriske lidelser 3,4 .Current Farmakoterapeutisk behandlinger har begrænset effekt og er forbundet med mange skadelige bivirkninger 5,6. Derfor er en bedre forståelse af patofysiologien af ​​denne lidelse sideløbende med udviklingen af ​​innovative og forbedrede behandlinger fortsat af afgørende betydning. Derfor dyremodeller er afgørende for at fremme forskning på dette område. Der er mange modeller, der anvendes til undersøgelse af denne lidelse (&lt;em&gt; fx saccharose præference test, hale suspension test) med test med tvungen svømning (FST, også kendt som Porsolts test efter udvikleren af denne model 7,8) er en af de mest almindeligt anvendte assays 7,9-12. Under FST et dyr er placeret i en beholder fyldt med vand, hvorfra det ikke kan slippe ud. Dyret vil først forsøge at flygte, men i sidste ende vil udvise immobilitet (dvs. flydende med fraværet af enhver bevægelse bortset fra nødvendigt for at holde næsen oven vande). FST er en meget populær model i dyreforsøg for en række årsager. For det første indebærer eksponering af dyrene til stress, som viste sig at have en rolle i tendensen til større depression 12-14. Desuden depression er ofte ses som en manglende evne til at håndtere stress 15-17. For det andet har vist farmakologisk behandling med antidepressiva før testen for at reducere immobilitet i FST &lt;sup&gt; 18-23. Derfor er det ofte brugt som en screening assay for nye forbindelser med potentielle antidepressive egenskaber 15-17,24. Derudover er FST vist sig at dele nogle af de faktorer, der er påvirket eller ændret af depression hos mennesker, såsom ændringer i fødevareforbruget, søvnforstyrrelser og lægemiddel-tilbagetrækning-induceret anhedonia 15-17,24. Dette er også grunden til, at denne test er undertiden anvendes til at vurdere depressive-lignende adfærd i mutante mus, med stigning eller fald i basal immobilitet (sammenlignet med &quot;vildtype&quot; mus) 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.

De følgende resultater er baseret på offentliggjorte data fra vores laboratorium. I dette forsøg blev voksen ICR hunmus testet efter 3 ugers behandling med selektive serotonin reuptake inhibitor (SSRI) escitalopram eller en ny urte anti-depressiv og anti-angst behandling (NHT) (for yderligere oplysninger om urte behandling, se 12 , 27,28). One-way ANOVA viste, at behandlingen reducerede depressive-lignende adfærd i FST [F (2,58) = 4,88, p &lt;0,05]. Ensidig Dunnet analyse afslørede, at behandling med ent...

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.

Den tvungne Swim Test som en model af depressive-lignende opførsel

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

Research

JoVE Journal

Behavior

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illustrated using artistic drawings. The use of the resident intruder paradigm for acute and chronic social stress experiments is explained as well. Finally, some brief tests and criteria are presented to distinguish aggression from its more violent and pathological forms.

This video shows the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression, defensive behavior and violence in a semi-natural setting. The use of the paradigm for social stress experiments is explained as well.

Resident-ubuden gæst Paradigm: en standardiseret test for Aggression, vold og social Stress

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to ...

Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most common method for assessing exercise endurance in mice utilizes forced running on a motorized treadmill equipped with a shock grid. Animals who quit running are pushed by the moving treadmill belt onto a grid that delivers an electric foot shock; to escape the negative stimulus, the mice return to running on the belt. However, avoidance behavior and psychological stress due to use of a shock apparatus can interfere with quantitation of running endurance, as well as confound measurements of postexercise serum hormone and cytokine levels. Here, we demonstrate and validate a refined method to measure running endurance in na&#239;ve C57BL/6 laboratory mice on a motorized treadmill without utilizing a shock grid. When mice are preacclimated to the treadmill, they run voluntarily with gait speeds specific to each mouse. Use of the shock grid is replaced by gentle encouragement by a human operator using a tongue depressor, coupled with sensitivity to the voluntary willingness to run on the part of the mouse. Clear endpoints for quantifying running time-to-exhaustion for each mouse are defined and reflected in behavioral signs of exhaustion such as splayed posture and labored breathing. This method is a humane refinement which also decreases the confounding effects of stress on experimental parameters.

A method to assess exercise endurance in laboratory mice without the use of a shock grid is demonstrated. This method is a humane refinement that can decrease the confounding effects of stress on experimental parameters.

Vurdering af murine Motion Endurance uden brug af et chok Grid: Et alternativ til tvungen Motion

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most ...

The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

Environmental enrichment can dramatically influence the development and function of neural circuits. Further, enrichment has been shown to successfully delay the onset of symptoms in models of Huntington&#8217;s disease 1-4, suggesting environmental factors can evoke a neuroprotective effect against the progressive, cellular level damage observed in neurodegenerative disorders. The ways in which an animal can be environmentally enriched, however, can vary considerably. Further, there is no straightforward manner in which the effects of environmental enrichment can be assessed: most methods require either fairly complicated behavioral paradigms and/or postmortem anatomical/physiological analyses. This protocol describes the use of a simple and inexpensive behavioral assay, the Puzzle Box 5-7 as a robust means of determining the efficacy of increased social, sensory and motor stimulation on mice compared to cohorts raised in standard laboratory conditions. This simple problem solving task takes advantage of a rodent&#8217;s innate desire to avoid open enclosures by seeking shelter. Cognitive ability is assessed by adding increasingly complex impediments to the shelter&#8217;s entrance. The time a given subject takes to successfully remove the obstructions and enter the shelter serves as the primary metric for task performance. This method could provide a reliable means of rapidly assessing the efficacy of different enrichment protocols on cognitive function, thus paving the way for systematically determining the role specific environmental factors play in delaying the onset of neurodevelopmental and neurodegenerative disease.

Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple &#8220;Puzzle Box&#8221; method for assessing an animal&#8217;s cognitive function, in order to reveal the effectiveness of environmental enrichment.

Brugen af ​​Puzzle Box som et middel til vurdering af effektiviteten af ​​miljøberigelse

Environmental enrichment can dramatically influence the development and function of neural circuits.  Further, enrichment has been shown to successfully ...

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti- or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.

The goal of the protocol described in this paper is to induce compulsive-like behavior in rats for the study of obsessive-compulsive disorder (OCD). This behavior is precipitated by attenuating a signal indicating that a lever-press response was effective in producing food.

Signaldæmpning som en rottemodel for Obsessive Compulsive Disorder

In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus ...

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

Paw-Trække: en roman, Sensitive Analyse af Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

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).

Den sociale dimension af stress: Eksperimentelle manipulationer af social støtte og social identitet i Trier Social stresstesten

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

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images.
Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer&#39;s disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI).
The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus.
4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of &#8804;8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55).
In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer&#039;s Disease

This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD.

Den 4 Mountains Test: en kort test af rumlig hukommelse med høj følsomhed for Diagnose af Pre-demens Alzheimers sygdom

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

Den gnaver Psykomotorisk Årvågenhed Test (rPVT): en metode til vurdering neurobehavioral Performance i rotter og mus

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster

An individual's sexual drive is influenced by genotype, experience and environmental conditions. How these factors interact to modulate sexual behaviors remains poorly understood. In Drosophila melanogaster, environmental cues, such as food availability, affect mating activity offering a tractable system to investigate the mechanisms modulating sexual behavior. In D. melanogaster, environmental cues are often sensed via the chemosensory gustatory and olfactory systems. Here, we present a method to test the effect of environmental chemical cues on mating behavior. The assay consists of a small mating arena containing food medium and a mating couple. The mating frequency for each couple is continuously monitored for 24 h. Here we present the applicability of this assay to test environmental compounds from an external source through a pressurized air system as well as manipulation of the environmental components directly in the mating arena. The use of a pressurized air system is especially useful to test the effect of very volatile compounds, while manipulating components directly in the mating arena can be of value to ascertain a compound's presence. This assay can be adapted to answer questions about the influence of genetic and environmental cues on mating behavior and fecundity as well as other male and female reproductive behaviors.

A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster

We demonstrate an assay to analyze the environmental and genetic cues that influence mating behavior in the fruit fly Drosophila melanogaster.

En metode til at teste effekten af ​​miljøvinkler på parringsadfærd i<em&gt; Drosophila melanogaster</em

An individual's sexual drive is influenced by genotype, experience and environmental conditions. How these factors interact to modulate sexual behaviors ...

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.

En to-interval tvunget valg opgave for multisensoriske sammenligninger

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