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FORCED SWIMMING TEST:
NEW FST DUAL SENSOR
(Model: BIO-FST-DSR - For rats)
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 I.Mendez-David, JP. Guilloux, M. Papp, L. Tritschler, E. Mocaer, A. Gardier, S. Bretin, D. David in "Frontiers in Pharmacology" highlights the merits of using Bioseb's Forced Swimming Test: New FST DUAL SENSOR: S 47445 Produces Antidepressant- and Anxiolytic Like Effects through Neurogenesis Dependent and Independent Mechanisms

S 47445 Produces Antidepressant- and Anxiolytic Like Effects through Neurogenesis Dependent and Independent Mechanisms
I.Mendez-David, JP. Guilloux, M. Papp, L. Tritschler, E. Mocaer, A. Gardier, S. Bretin, D. David
Institut de Recherches Internationales Servier, Suresnes, France
Published in "Frontiers in Pharmacology" (2017-07-19)


Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor's (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively) were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM), open field (OF), splash test (ST), forced swim test (FST), tail suspension test (TST), fur coat state and novelty suppressed feeding (NSF) as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.). In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p.) during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model), neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state's deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg) seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg) and EPM (from 1 mg/kg). In the CMS rat model, S 47445(from 1 mg/kg) demonstrated a rapid onset of effect on anhedonia compared to venlafaxine and imipramine. In the CORT model, S 47445 demonstrated significant neurogenic effects on proliferation, survival and maturation of hippocampal newborn neurons at doses inducing an antidepressant-like effect. It also corrected CORT-induced deficits of growth and arborization of dendrites. Finally, the antidepressant/anxiolytic-like activities of S 47445 required adult hippocampal neurogenesis in the novelty suppressed feeding test contrary to OF, EPM and ST. The observed increase in hippocampal BDNF levels could be one of the mechanisms of S 47445 responsible for the adult hippocampal neurogenesis increase. Altogether, S 47445 displays robust antidepressant-anxiolytic-like properties after chronic administration through neurogenesis dependent/independent mechanisms and neuroplastic activities. The AMPA-PAM S 47445 could have promising therapeutic potential for the treatment of major depressive disorders or generalized anxiety disorders.
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.

NEURODEGENERATION
- Huntington's disease -
Huntingtin Acts Non Cell-Autonomously on Hippocampal Neurogenesis and Controls Anxiety-Related Behaviors in Adult Mouse (-1)
Huntingtin Acts Non Cell-Autonomously on Hippocampal Neurogenesis and Controls Anxiety-Related Behaviors in Adult Mouse
P. Pla, S. Orvoen, C. Benstaali, S. Dodier, D. J. David et al.
Université Paris-Sud, Orsay, France
Published in "PLOS One" (0000-00-00)

Huntington’s disease (HD) is a fatal neurodegenerative disease, characterized by motor defects and psychiatric symptoms, including mood disorders such as anxiety and depression. HD is caused by an abnormal polyglutamine (polyQ) expansion in the huntingtin (HTT) protein. The development and analysis of various mouse models that express pathogenic polyQ-HTT revealed a link between mutant HTT and the development of anxio-depressive behaviors and various hippocampal neurogenesis defects. However, it is unclear whether such phenotype is linked to alteration of HTT wild-type function in adults. Here, we report the analysis of a new mouse model in which HTT is inducibly deleted from adult mature cortical and hippocampal neurons using the CreERT2/Lox system. These mice present defects in both the survival and the dendritic arborization of hippocampal newborn neurons. Our data suggest that these non-cell autonomous effects are linked to defects in both BDNF transport and release upon HTT silencing in hippocampal neurons, and in BDNF/TrkB signaling. The controlled deletion of HTT also had anxiogenic-like effects. Our results implicate endogenous wild-type HTT in adult hippocampal neurogenesis and in the control of mood disorders.

MOOD DISORDERS
- Depression -
S 47445 Produces Antidepressant- and Anxiolytic Like Effects through Neurogenesis Dependent and Independent Mechanisms (2017)
S 47445 Produces Antidepressant- and Anxiolytic Like Effects through Neurogenesis Dependent and Independent Mechanisms
I.Mendez-David, JP. Guilloux, M. Papp, L. Tritschler, E. Mocaer, A. Gardier, S. Bretin, D. David
Institut de Recherches Internationales Servier, Suresnes, France
Published in "Frontiers in Pharmacology" (2017-07-19)

Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor's (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively) were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM), open field (OF), splash test (ST), forced swim test (FST), tail suspension test (TST), fur coat state and novelty suppressed feeding (NSF) as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.). In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p.) during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model), neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state's deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg) seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg) and EPM (from 1 mg/kg). In the CMS rat model, S 47445(from 1 mg/kg) demonstrated a rapid onset of effect on anhedonia compared to venlafaxine and imipramine. In the CORT model, S 47445 demonstrated significant neurogenic effects on proliferation, survival and maturation of hippocampal newborn neurons at doses inducing an antidepressant-like effect. It also corrected CORT-induced deficits of growth and arborization of dendrites. Finally, the antidepressant/anxiolytic-like activities of S 47445 required adult hippocampal neurogenesis in the novelty suppressed feeding test contrary to OF, EPM and ST. The observed increase in hippocampal BDNF levels could be one of the mechanisms of S 47445 responsible for the adult hippocampal neurogenesis increase. Altogether, S 47445 displays robust antidepressant-anxiolytic-like properties after chronic administration through neurogenesis dependent/independent mechanisms and neuroplastic activities. The AMPA-PAM S 47445 could have promising therapeutic potential for the treatment of major depressive disorders or generalized anxiety disorders.

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.

Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice (2013)
Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice
Jean-Philippe Guillouxa, Indira Mendez-Davida, Alan Pehrsonb, Bruno P. Guiard et al.
Univ. Paris-Sude, France - Lundbeck Research, USA
Published in "Neuropharmacology Volume 73" (2013-10-30)

Vortioxetine (Lu AA21004) is an investigational novel antidepressant with multimodal activity that functions as a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we explore its anxiolytic and antidepressant potential in adult mice. Vortioxetine was assessed in BalB/cJ@RJ mice using the open-field and forced-swim tests (acute: p.o. 1 h, repeated: daily p.o. 21 days), and in 129S6/SvEvTac mice using the novelty suppressed feeding paradigm (acute: p.o. 1 h, sustained: daily p.o. 14 or 21 days). Fluoxetine and diazepam were controls. Acute and repeated dosing of vortioxetine produced more pronounced anxiolytic- and antidepressant-like activities than fluoxetine. Vortioxetine significantly increased cell proliferation and cell survival and stimulated maturation of immature granule cells in the subgranular zone of the dentate gyrus of the hippocampus after 21 days of treatment. After 14 days, a high dose of vortioxetine increased dendritic length and the number of dendrite intersections, suggesting that vortioxetine accelerates the maturation of immature neurons. Vortioxetine displays an antidepressant and anxiolytic profile following repeated administration associated with increased neurogenesis at several stages. Vortioxetine effects were observed at low levels of 5-HT transporter occupancy, suggesting an alternative mechanism of action to 5-HT reuptake inhibition.

Depressive-like behaviours and decreased dendritic branching in the medial prefrontal cortex of mice with tumors: A novel validated model of cancer-induced depression (-1)
Depressive-like behaviours and decreased dendritic branching in the medial prefrontal cortex of mice with tumors: A novel validated model of cancer-induced depression
Nashed MG, Seidlitz EP, Frey BN, Singh G
DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Canada.
Published in "Behav Brain Res." (0000-00-00)

Depression is commonly comorbid in cancer patients and has detrimental effects on disease progression. Evidence suggests that biological mechanisms may induce the onset of cancer-induced depression (CID). The present investigation aims to establish a validated preclinical animal model of CID. Female BALB/c mice were allocated to four groups: control (n=12), chronic oral exposure to corticosterone (CORT) (n=12), CORT exposure followed by chronic low dose fluoxetine (FLX) treatment (n=12), and subcutaneous inoculation of 4T1 mammary carcinoma cells (n=13). Anhedonia was evaluated using the sucrose preference test (SPT), and behavioural despair was evaluated using the forced swim test (FST) and tail suspension test (TST). Sholl analyses were used to examine the dendritic morphology of Golgi-Cox impregnated neurons from the medial prefrontal cortex (mPFC). CORT exposure and tumor burden were both associated with decreased sucrose preference, increased FST immobility, and decreased basilar and apical dendritic branching of neurons in the mPFC. CORT-induced behavioural and dendritic morphological changes were reversible by FLX. No differences in TST immobility were observed between groups. On the secondary TST outcome measure, CORT exposure and tumor burden were associated with a trend towards decreased power of movement. CORT exposure induced a positive control model of a depressive-like state, with FLX treatment confirming the predictive validity of the model. This verified the sensitivity of behavioural and histological tests, which were used to assess the CID model. The induction of a depressive-like state in this model represents the first successfully validated animal model of CID.



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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-DSR
Forced Swimming Test: New FST DUAL SENSOR (Modif.)
For rats Contact us

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Accessories :
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BIO-FST-BKM
Additional beaker for mice (Modif.)
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