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FORCED SWIMMING TEST:
NEW FST DUAL SENSOR
(Model: BIO-FST-DSM - For mice)
The new Forced Swimming Test system from Bioseb uses a dual approach:
Combining a double input from vibrations and video,
the TYC (Train-Your-Computer) algorithm compares both inputs to determine the animal's behavior in real time, making results completely operator-independent.

Experiment manager, analysis module, replay possibilities and the TYC algorithm are some of the features that make FST DUAL SENSOR a very innovative and easy to use instrument for both mice or rats studies (up to 4 animals can be tested at a time), based on the famous Porsolt Test, or "behavioral despair" test


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  • CNRS Valbonne, France
  • SWISSFEDERAL INSTITUTE OF TECHNOLOGY Lausanne, Suisse
  • THE PENNSYLVANIA STATE UNIVERSITY University Park, Etats-Unis
  • UNIVERSITY OF ILLINOIS AT URBANA Urbana, Etats-Unis
  • FACULTY OF MEDECINE ROUEN, FRANCE
  • INSTITUT PASTEUR PARIS, FRANCE
  • FACULTY OF PHARMACY PARIS, FRANCE
  • KU LEUVEN BRUSSELS, BELGIUM
  • Instytut Biologii UMCS LUBLIN, POLAND
  • UNIVERSITE PARIS SUD PARIS, France
  • CNRS ROUEN, France
  • EPFL Lausanne, France
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! NEW RESEARCH WORK ! A recent publication by E Ahmed, MK Tawfik, SS Essawy, AS Ahmed et al in "Egyptian Journal of Basic and Clinical Pharmacology" highlights the merits of using Bioseb's Forced Swimming Test: New FST DUAL SENSOR: Cysteamine Potentiates the Anti-Depressive Effects of Venlafaxine in Corticosterone-Induced Anxiety/Depression Mouse Model: Effect on Brain-Derived Neurotrophic

Cysteamine Potentiates the Anti-Depressive Effects of Venlafaxine in Corticosterone-Induced Anxiety/Depression Mouse Model: Effect on Brain-Derived Neurotrophic
E Ahmed, MK Tawfik, SS Essawy, AS Ahmed et al
Neuropharmacology Group, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
Published in "Egyptian Journal of Basic and Clinical Pharmacology" (2018-09-10)


The hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been linked to the occurrence of severe depressive and anxiety states. Venlafaxine, a serotonin and a noradrenaline reuptake inhibitor (SNRI), is an approved antidepressant agent with evidence of non-response to treatment in a subset of patients. In this study, 48 male mice (30-38 g) were used to evaluate the possible anxiolytic and antidepressant in_uence of intraperitoneal (i.p.) cysteamine (150 mg/kg/day) on i.p. venlafaxine (10mg/Kg and 20mg/Kg), as well as e_ects on brain-derived neurotrophic factor (BDNF) level and tropomyosin-related kinase B (TrkB) gene expression in prefrontal cortex (PFC) in corticosterone-induced anxiety/depression mouse model. The present results provided evidence on insu_cient venlafaxine anxiolytic and antidepressant e_ects in this model. However, cysteamine combined with venlafaxine caused signi_cant antidepressant behavioral e_ects together with a signi_cant increase in BDNF levels followed by TrkB receptor downregulation in mice PFC. In conclusion, we highlight the potential use of a combination therapy of venlafaxine and cysteamine as a therapeutic strategy for glucocorticoid-related symptoms of depression
Presentation

The Forced Swimming Test (FST), also known as Porsolt Swimming Test or "behavioral despair test", is a common behavioral test for the development and screening of antidepressant and anxiolytic drugs to identify new treatments and understand the biological mechanisms of current treatments.

Bioseb's Forced Swimming Test FST DUAL SENSOR has been designed for rats and mice thanks to the expert work of Dr. Denis DAVID (described in a publication in NEURON in 2009, "Neurogenesis Dependent and Independent Effects of Fluoxetine in an Animal Model of Anxiety/Depression").

Operating principle:

What is the TYC algorithm of Bioseb's new Forced Swimming Test ?
• A new tool that gives the researcher total control when evaluating protocols.
• The researcher is the expert!
• The TYC is taught how to detect the 3 states: Resting/Floating, Swimming, and Climbing/Struggling

The scoring can be learned and then consistently applied with no variability and drift over time! The TYC algorithm is an optimization tool: with a single run manually evaluated by the researcher, one will train the software to use scored parameters, TYC will adjust scoring algorithms to follow the researcher's evaluation rules.
The system allows easy comparison of several approaches, useful in training students, and provides consistency across multiple studies.

Two types of behavior can be observed during the Porsolt Test using FST DUAL SENSOR:

1. Non-depressed rodents (rats or mice), even when unable to escape from the water-filled cylinders, will try to swim and struggle to escape the containers.
2. Depressed rodents will stop trying sooner than non-depressed rodents and start to float in the cylinders, showing behavioural despair.

The floating or immobility time during the forced swimming test is an accurate indication of the effects of anti-depressants and anxiolitics.

Features

Bioseb offers a powerful dual approach system based on vibrations detection and video-based motor activity analysis for automating the Porsolt Forced Swimming Test. Using the state-of-the-art video tracking algorithms combined with each beaker vibration, the software solution allows the researcher to analyse and separate different behaviours via a calibration process that learned from an expert in the lab.
Up to 4 animals (mouse or rat) can be tested simultaneously. A manual set-up would only allow the assessment of 1 animal at a time.

Using the FST DUAL SENSOR, the researcher will be able to record video of the trials, calculate the immobility time, swimming time, and struggling time for each animal tested and do so in batches of four. Each acquisition can be replayed and re-analyzed later with different settings : thus, a calibration made by an expert from another lab could be used as well. Results can be exported to any software of choice for further analysis.

The management of the Porsolt Forced Swimming Test experiment is facilitated via a list of animals that can be entered into the software or imported from excel. Several possibilities for randomization are presented, and the randomized list can be exported, imported, and printed. Runs can be paused or started at any time.

Bioseb's Forced Swimming Test (Porsolt): New FST X'PERT - Software screenshot Bioseb's Forced Swimming Test (Porsolt): New FST X'PERT - Software screenshot - Results
Bioseb's Forced Swimming Test (Porsolt): New FST DUAL SENSOR - Software screen-shots

Parameters measured

The BIOSEB Forced Swimming Test FST DUAL SENSOR solution allow automatic computing of three parameters or states for the rats and the mice:

• Swimming
• Non-active (immobility, passive floating)
• Climbing/struggling
• Dipping (rat only) which can be easily set manually when analysing the files
Results are organized by groups or individual animal, and can be displayed for every minute of the test.

Domains of application

• Review of antidepressant activity
• Primary screening test for antidepressants
• Evaluation of psycho-stimulants
• Evaluation of anxiety treatments

Examples of Agents used are Imiprimine, Fluoxetine, Desipramine, and Venlafaxine.

Options

• BIO-FST-BKR Instrumented Spare beaker for rats (30 cm diameter x 50 cm height)
• BIO-FST-BKM Instrumented Spare beaker for mice (17 cm diameter x 20 cm height)

Supplied with

• A customized support frame that separates the four beakers, houses the interface and supports the HD camera
• Four graduated beakers for rats or mice, (30 cm diameter for rats, 17 cm diameter for mice; extras available upon request)
• An FST DUAL SENSOR software product with license
• User's manual



Publications (Click on an article to show details and read the abstract)

PAIN
- General pain -
Antinociceptive and antidepressant-like action of endomorphin-2 analogs with proline surrogates in position 2 (2014)
Antinociceptive and antidepressant-like action of endomorphin-2 analogs with proline surrogates in position 2
Perlikowska R, Piekielna J, Mazur M, Koralewski R, Olczak J, do Rego JC, Fichna J, Modranka J, Janecki T, Janecka A
Medical University of Lodz, Lodz, Poland
Published in "Bioorg Med Chem." (2014-09-01)

In our efforts to develop new candidate drugs with antinociceptive and/or antidepressant-like activity, two novel endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH2) analogs, containing proline surrogates in position 2 were synthesized using commercially available racemic trans-4-phenylpyrrolidine-3-carboxylic acid (4-Ph-?-Pro). The obtained mixture of two diastereoisomeric peptides (2a and 2b) was separated by HPLC and both enantiopure analogs were used in the in vitro and in vivo studies. To assign the absolute configuration to the 4-Ph-?-Pro residues in both peptides, the stereoselective synthesis of (3R,4S)-4-phenylpyrrolidine-3-carboxylic acid was performed and this enantiomer was introduced into position 2 of EM-2 sequence. Based on the HPLC retention times we were able to assign the absolute configuration of 4-Ph-?-Pro residues in both peptide analogs. Analog 2a incorporating (3R,4S)-4-Ph-?-Pro residue produced strong analgesia in mice after intracerebroventricular (icv) administration which was antagonized by the ?-opioid receptor (MOR) antagonist, ?-funaltrexamine (?-FNA). This analog also influenced an emotion-related behavior of mice, decreasing immobility time in the forced swimming and tail suspension tests, without affecting locomotor activity. The antidepressant-like effect was reversed by the ?-selective antagonist, naltrindole (NLT) and ?-selective nor-binaltorphimine (nor-BNI). Thus, the experiments with selective opioid receptor antagonists revealed that analgesic action of analog 2a was mediated through the MOR, while the ?- and ?-receptors (DOR and KOR, respectively) were engaged in the antidepressant-like activity. Analog 2b with (3S,4R)-4-Ph-?-Pro in position 2 showed no antinociceptive or antidepressant-like activity in animal studies.

Effect of potent endomorphin degradation blockers on analgesic and antidepressant-like responses in mice. (2011)
Effect of potent endomorphin degradation blockers on analgesic and antidepressant-like responses in mice.
A. Cravezic, J. Fichna, K. Gach, A. Wyrebska, R. Perlikowska et al.
University of Rouen, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, IFRMP23, Mont-Saint-Aignan, France.
Published in "Neuropharmacology" (2011-12-01)

The biological effects of endomorphins (EMs) are short-lasting due to their rapid degradation by endogenous enzymes. Competing enzymatic degradation is an approach to prolong EM bioavailability. In the present study, a series of tetra- and tripeptides of similar to EMs structure was synthesized and tested in vitro and in vivo for their ability to inhibit degradation of EMs. The obtained results indicated that, among the series of analogs, the tetrapeptide Tyr-Pro-d-ClPhe-Phe-NH(2) and the tripeptide Tyr-Pro-Ala-NH(2), which did not bind to the _-opioid receptors, were potent inhibitors of EM catabolism in rat brain homogenate. In vivo, these two peptides significantly prolonged the analgesic and antidepressant-like effects, induced by exogenous EMs, by blocking EM degrading enzymes. These new potent inhibitors may therefore increase the level and the half life of endogenous EMs and could be used in a new therapeutic strategy against pain and mood disorders, based on increasing of EM bioavailability.

NEURODEGENERATION
- Huntington's disease -
Huntington's disease knock-in male mice show specific anxiety-like behaviour and altered neuronal maturation. (2012)
Huntington's disease knock-in male mice show specific anxiety-like behaviour and altered neuronal maturation.
S. Orvoen, P. Pla, A. Gardier, F. Saudou, D. David.
Univ Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
Published in "Neuroscience Letters" (2012-01-24)

Huntington's disease (HD) is a devastating genetic neurodegenerative disorder. Major depressive disorder and more generally mood disorders are a major component of the symptoms during the pre-motor symptomatic stages of the disease. We report here that knock-in Hdh(Q111) mice, an animal model of HD, that carry an expanded polyglutamine stretch in the mouse HD protein show an anxio-depressive-like phenotype prior to any impairment of the locomotor function. Strikingly, whereas females develop preferentially a depressive-like behaviour, males had an increased anxiety-like phenotype. Since adult hippocampal neurogenesis has been associated to the pathophysiology and treatment of depression, we investigated whether changes in behavioural phenotypes are associated with proliferation or maturation impairments. Whereas cell proliferation was not affected in knock-in Hdh(Q111) mice, a male-specific marked decrease in late maturation of newborn neurons was observed in the adult dentate gyrus. Together, our results highlight sex differences in both behaviour and adult neurogenesis in a knock-in model of HD.

MOOD DISORDERS
- Anxiety -
Evaluation of anxiolytic-like, anticonvulsant, antidepressant-like and antinociceptive properties of new 2-substituted 4-hydroxybutanamides with affinity for GABA transporters in mice (2013)
Evaluation of anxiolytic-like, anticonvulsant, antidepressant-like and antinociceptive properties of new 2-substituted 4-hydroxybutanamides with affinity for GABA transporters in mice
K. Sałata, K. Kuligb, J. Gajdab, K. Więckowskib, B. Filipeka et al.
Jagiellonian University, Medical College, Cracow, Poland
Published in "Pharmacology Biochemistry and Behavior" (2013-07-10)

Purpose
The inhibition of plasma membrane GABA transporters (GATs) is responsible for anxiolytic-like, anticonvulsant, antinociceptive and antidepressant-like effects in mice. It also influences animals' motor coordination and their sensitivity to ethanol. The aim of this study was to assess the pharmacological activity of two novel 2-substituted 4-hydroxybutanamides (BM 130 and BM 131) in some screening models. An attempt has been made to establish the relationship between the inhibition of GAT subtype and the observed in vivo activity.
Methods
The affinity for GAT subtypes was evaluated by means of [3H]GABA uptake assay. It indicated that BM 130 inhibited GAT1 and GAT2, whereas BM 131 inhibited GAT1 and GAT3. In mice anxiolytic-like, antidepressant-like, anticonvulsant and antinociceptive properties of the test compounds were assessed. Their influence on motor coordination, locomotor activity and the ability to potentiate effects of subnarcotic doses of ethanol was also tested.
Results
Both compounds administered intraperitoneally exerted a significant anxiolytic-like effect in the four plate test with ED50 values 3.4 and 7.9 mg/kg, respectively. At 30 mg/kg they reduced duration of immobility in the forced swim test for 33% and 19%, respectively. They had no effect on electroconvulsive threshold or pain reactivity in the hot plate assay but they were antinociceptive in the acetic acid-induced writhing test (ED50 values were 12.7 and 18.6 mg/kg, respectively) and in both phases of the formalin test (ED50 values in the first phase were 10.2 and 2.1 mg/kg for BM 130 and BM 131, respectively). No motor adverse effects were observed in mice pretreated with the test compounds in the rotarod or chimney tests but BM 131 caused a transient but statistically significant decrease of animals' locomotor activity.
Conclusions
In mice BM 130 and BM 131 have anxiolytic-like, antidepressant-like and antinociceptive properties which can be attributed to their affinity for not only mGAT1 but also mGAT2–4.

Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. (2011)
Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety.
Q. Rainer, L. Xia, JP. Guilloux, C. Gabriel, DJ. David et al
Université Paris-Sud, Laboratoire Neuropharmacologie, Châtenay-Malabry, France.
Published in "International journal of neuropsychology" (2011-01-26)

Agomelatine (S20098) is a novel antidepressant drug with melatonergic agonist and 5-HT2C receptor antagonist properties, displaying antidepressant/anxiolytic-like properties in animal models and in humans. In a depression/anxiety-like mouse model in which the response of the HPA axis is blunted, we investigated whether agomelatine could reverse behavioural deficits related to depression/anxiety compared to the classical selective serotonin reuptake inhibitor, fluoxetine. Adult mice were treated for 8 wk with either vehicle or corticosterone (35 μg/ml.d) via drinking water. During the final 4 wk, animals were treated with vehicle, agomelatine (10 or 40 mg/kg i.p.) or fluoxetine (18 mg/kg i.p.) and tested in several behavioural paradigms and also evaluated for home-cage activity. Our results showed that the depressive/anxiety-like phenotype induced by corticosterone treatment is reversed by either chronic agomelatine or fluoxetine treatment. Moreover, agomelatine increased the dark/light ratio of home-cage activity in vehicle-treated mice and reversed the alterations in this ratio induced by chronic corticosterone, suggesting a normalization of disturbed circadian rhythms. Finally, we investigated the effects of this new antidepressant on neurogenesis. Agomelatine reversed the decreased cell proliferation in the whole hippocampus in corticosterone-treated mice and increased maturation of newborn neurons in both vehicle- and corticosterone-treated mice. Overall, the present study suggests that agomelatine, with its distinct mechanism of action based on the synergy between the melatonergic agonist and 5-HT2C antagonist properties, provides a distinct antidepressant/anxiolytic spectrum including circadian rhythm normalization.

- Depression -
Cysteamine Potentiates the Anti-Depressive Effects of Venlafaxine in Corticosterone-Induced Anxiety/Depression Mouse Model: Effect on Brain-Derived Neurotrophic (2018)
Cysteamine Potentiates the Anti-Depressive Effects of Venlafaxine in Corticosterone-Induced Anxiety/Depression Mouse Model: Effect on Brain-Derived Neurotrophic
E Ahmed, MK Tawfik, SS Essawy, AS Ahmed et al
Neuropharmacology Group, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
Published in "Egyptian Journal of Basic and Clinical Pharmacology" (2018-09-10)

The hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been linked to the occurrence of severe depressive and anxiety states. Venlafaxine, a serotonin and a noradrenaline reuptake inhibitor (SNRI), is an approved antidepressant agent with evidence of non-response to treatment in a subset of patients. In this study, 48 male mice (30-38 g) were used to evaluate the possible anxiolytic and antidepressant in_uence of intraperitoneal (i.p.) cysteamine (150 mg/kg/day) on i.p. venlafaxine (10mg/Kg and 20mg/Kg), as well as e_ects on brain-derived neurotrophic factor (BDNF) level and tropomyosin-related kinase B (TrkB) gene expression in prefrontal cortex (PFC) in corticosterone-induced anxiety/depression mouse model. The present results provided evidence on insu_cient venlafaxine anxiolytic and antidepressant e_ects in this model. However, cysteamine combined with venlafaxine caused signi_cant antidepressant behavioral e_ects together with a signi_cant increase in BDNF levels followed by TrkB receptor downregulation in mice PFC. In conclusion, we highlight the potential use of a combination therapy of venlafaxine and cysteamine as a therapeutic strategy for glucocorticoid-related symptoms of depression



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Technology Learning machine TYC algorithm, combines video tracking and vibrations
Dimensions (Lx W x H cm) 80 x 80 x 180 for the Rat version
60 x 60 x 120 for the Mouse version
Weight kg 24 kg for the Rat version
12 kg for the Mouse version
Power supply PC USB port
Graduated Beakers 4 x Transparent ACRYLIC type + sensors
30 cm diameter, 50 cm height for rats
17 cm diameter, 20 cm height for mice
Sensor calibration / repeatability After one-time initial calibration (6 min) : 4% variability
Wearable Part Instrumented beakers
Delivered with 4 instrumented beakers, standing unit, 1 HD USB camera, Software FST DUAL SENSOR, USB interface, mini USB cables, user’s manual.
Software BIO-FST Allows definition of 3 activity levels: Immobility, Swimming and Climbing (struggling).
Sampling Rate 300Hz, encrypted (glp) averaged and recorded synchronously with video images.
Replay and control At any time, remotely. Scoring tool included for calibration, may be used for training purpose and comparison with expert.
Results xls type, presented per rat/mouse or per groups & time period (every minutes)
PC Not supplied Requires 2GO RAM, Fast processor CORE I3, Windows 7, 8, 3x USB port
Option Extra Beaker

Model:
BIO-FST-DSM
Forced Swimming Test: New FST DUAL SENSOR
For mice Contact us

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