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TAIL SUSPENSION TEST - REINVENTED
(Model: BIO-TST4)
Bioseb's version 4 of the Tail Suspension Test system, based on both strain sensors and video acquisition, is the only fully automatic solution in the world for running a simple and objective despair test on mice. It is a fast, painless, and reliable way for testing psychotropic effects from stimulant doses of drugs such as anti-depressants and sedatives. This classic and painless research test for anxiety and depression is now offered with a a new, powerful and modern software.

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  • PORSOLT AND PARTNERS Boulogne, France
  • INSTITUT DE RECHERCHE SERVIER Croissy sur Seine, France
  • INSERM Paris, Creteil, France
  • HOWARD FLOREY INSTITUTE Melbourne, Australia
  • NOVARTIS Basel, Switzerland
  • ROCHE Basel, Switzerland
  • GLAXO SMITH KLINE UK
  • HELMHOLTZ ZENTRUM MÜNCHEN Neuherberg, Germany
  • GEDEON RICHTER Budapest, Hungaria
  • CENTER OF MENTAL HEALTH Mannheim,Germany
  • UNIVERSITY OF NANTES Nantes, France
  • CNRS Valbonne, Bordeaux, Rouen, France
  • SANOFY AVENTIS Bagneux, France
  • Swiss Federal Institute of Technology Lausanne, Suisse
  • UNIVERSITE PARIS SUD Chatenay Malabry, France
  • INSTITUTE OF EXPERIMENTAL MEDICINE Budapest, Hongrie
  • HELMHOLTZ ZENTRUM MÜNCHEN Neuherberg, Allemagne
  • SERVIER Croissy sur seine, France
  • INRA Bordeaux, France
  • IPSEN INNOVATION Les Ulis, France
  • LILLY TAIWAN
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! NEW RESEARCH WORK ! A recent publication by Z. Winkler, D. Kuti, S. Ferenczi, K. Gulyás, Á. Polyák, K. Kovács in "Behavioural Brain Research" highlights the merits of using Bioseb's Tail Suspension Test - Reinvented: Impaired microglia fractalkine signaling a?ects stress reaction and coping style in mice

Impaired microglia fractalkine signaling a?ects stress reaction and coping style in mice
Z. Winkler, D. Kuti, S. Ferenczi, K. Gulyás, Á. Polyák, K. Kovács
Institute of Experimental Medicine, Laboratory of Molecular Neuroendocrinology,Budapest, Hungary
Published in "Behavioural Brain Research" (2017-07-23)


Microglia, resident immune cells of the CNS are sensitive to various perturbations of the environment, such as stress exposure, and may be involved in translating these changes to behavior. Among the pathways mediating stress-related neuronal cues to microglia, the fractalkine-fractalkine receptor (CX3CR1) signaling plays a crucial role. Using mice, in which the CX3CR1 gene was deleted, we explored hormonal and behavioral responses to acute and chronic stress along with changes in hypothalamic microglia. CX3CR1-/- animals display active escape in forced swim- and tail suspension tests, exaggerated neuronal activation in the hypothalamic paraventricular nucleus and increased corticosterone release in response to restraint. Analysis of Iba1 immunostaining of hypothalamic sections revealed stress-related reduction of microglia in CX3CR1-/- mice. Because microglia also contribute to energy balance regulation, we characterized metabolic phenotype of CX3CR1-/- mice. Comparison of respiratory exchange ratio did not show genotype effect on fuel preference, however, the energy expenditure was increased in CX3CR1-/- mice, which may be related to their active coping behavior. Microglia and fractalkine signaling has been repeatedly shown to be involved chronic stress-induced depressive state. CX3CR1-/- mice did not become anhedonic in the "two hit" chronic stress paradigm, confirming resistance of these animals to chronic stress-induced mood alterations. However, there was no difference in stress hormone levels, open field performance and hypothalamic microglia distribution between the genotypes. These results highlight differential involvement of microglia fractalkine signaling in controlling/integrating hormonal-, metabolic and behavioral responses to acute and chronic stress challenges.

Fully automatic
Painless, "tape" technique
Tail Suspension Test by Bioseb: the suspension cages
Bioseb's Tail Suspension Cages
Presentation

The tail-suspension test was developed as an alternative to the Porsolt Forced Swimming test, and is based on a similar concept. Mice, suspended by their tail using a piece of tape (a painless method), innately attempt to escape from this adversive situation. However, following failed attempts to escape, they experience a kind of despair and become immobile. The magnitude of immobility is considered to be correlated with the depressive-like state of the subjects and is significantly decreased by antidepressants. The Tail Suspension Test was described in the 80's by Steru & al. and allows for fast evaluation of drugs' (anti-depressants, sedatives) psychotropic effects, making it a classic and painless research test for anxiety and depression.

BIOSEB' Tail Suspension Test system is the only full automatic test in the world!. It is based on the original “ITEMATIC-TST” described by Steru in 1987, it uses both strain gauges and video backup recording, and does not induce any pain in the animal: the mouse’s tail is simply stuck to the sensor using a piece of tape.

The original ITEMATIC design has been modified, adapted and improved for the Porsolt and Partners Pharmacology Co in the 2000. It can hold 3 mice in three separate compartments and features adjustable floor height and anti climbing plates for C57 strain mice.

The Bioseb Tail Suspension Test instrument offers unique features such as the randomization process of the animals, the measurement of up to 6 animals in the same run, the direct computations of the "Immobility", the "Energy" and the "Power in Motion". Settings are available to adjust the definitions to the user's protocol. The energy value is a unique way to differentiate between passive swinging and active struggling. The power in motion is an additional discriminating calculation that gives an indication of the strength of the mice.

How does it work?

Tail Suspension Test by Bioseb: painless tape fixing
Painless tape-based fixation
The measuring principle is based on the quantity of movements that a mouse trying to escape from its suspension can generate. During the Tail Suspension Test, the movements of the mice are analyzed in terms of activity (active/non active), energy and power developed over time. As human observation is time consuming and tedious, Bioseb's Tail Suspension Test (TST) automates the entire experiment.

The operator prepares his pieces of tape to suspend mice and the home cages with mice to be tested. When the whole experiment has been setup in the software and the list of animals randomized, the operator suspends each single mouse according to the randomization shown on the screen. Each channel is started individually by pressing a specific key on the computer so that each mouse is suspended the same amount of time (something impossible with a system based solely on video).

When the run is finished, mice are removed and the operator is prompted to suspend the next batch of mice. After the experiment, the whole batch can be analyzed and statistics on averages minimums, maximums and standard deviations are computed in seconds as is individual performance. Data is also presented within minutes for both the groups and individual animals (mice).

The TST-SOFT generates graphics that can be exported as a bmp image for further presentations.

Key features

• Fully automatic and operator-independent
• Includes 4 types of randomization processes of the animal list
• Measurement of up to 6 animals in the same run
• Full control of the calibration
• High predictability for antidepressant effects in humans
• Based on innate behaviours and despair models
• Widely used in literature and deeply validated in phenotyping and pharmacology
• Simple to set up and use
• Replay possible with other parameters
• Short-lasting experiment (usually 6 minutes)
• Optional video recording to adjust the activity threshold
Domains of application

• Depression & anxiety
• Drug screening
• Basal depressive-like state phenotyping
• Studies on behavioral abnormalities
• Behavioral effects of pharmacological compounds relevant to depression
• Antidepressant efficacy on chronic stress models
• Sleep and mood disorders
• Studies on serotonin aspects
• Acupuncture and dopamine
• Behavioral effects of genetic manipulations relevant to depression

Software & parameters measured

The brand new software for Bioseb’s Tail Suspension test is based on direct acquisition from the strain sensors, as well as video monitoring. It is powerful, yet flexible and user-friendly.

• Just one screen is needed to set up all the parameters such as the number of animals, thresholds, and starting and ending times of the measuring period.
• The animal list can be edited, exported, or imported from excel or csv format directly.
• The "Randomization" module defines the order of the different "dosed" animals with their groups.
• During the test, a bargraph displays energy and the real time computation of results.
• The results for immobility time, energy value, and power during the mobility period are displayed via graphs and numerical tables.
• Original Data files are saved and protected in a GLP compatible format.
• Replay of past experiments is always possible, allowing testing of different parameters.
• It is possible to discard the result of a particular animal (for example if the subject falls down during the test), in order to secure traceability.
• A manual scoring module used together with a camera can be used to determine the type of threshold the operator should set in the system.

Screenshot of Bioseb's new Tail Suspension Test software for Drug Screening, Anxiety and Depression Screenshot of Bioseb's new Tail Suspension Test software for Drug Screening, Anxiety and Depression
Screenshots of Bioseb's new Tail Suspension Test software

Supplied with

• One or two sets of three cages together with power supplies and USB cables as needed.
• 1 software license (USB dongle with product ID tag)
• Optional HD USB camera and its tripod and USB cable

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.

- Neuropathic pain -
Stress-Induced Anhedonia in Mice is Associated with Deficits in Forced Swimming and Exploration. (2004)
Stress-Induced Anhedonia in Mice is Associated with Deficits in Forced Swimming and Exploration.
T. Strekalova, R. Spanagel, D. Bartsch, F. A. Henn, P. Gass.
University of Heidelberg, Central Institute of Mental Health, Mannheim, Germany.
Published in "Neuropsychopharmacology" (2004-11-30)

In order to develop a model for a depression-like syndrome in mice, we subjected male C57BL/6 mice to a 4-week-long chronic stress procedure, consisting of rat exposure, restraint stress, and tail suspension. This protocol resulted in a strong decrease in sucrose preference, a putative indicator of anhedonia in rodents. Interestingly, predisposition for stress-induced anhedonia was indicated by submissive behavior in a resident–intruder test. In contrast, most mice with nonsubmissive behavior did not develop a decrease in sucrose preference and were regarded as nonanhedonic. These animals were used as an internal control for stress-induced behavioral features not associated with the anhedonic state, since they were exposed to the same stressors as the anhedonic mice. Using a battery of behavioral tests after termination of the stress procedure, we found that anhedonia, but not chronic stress per se, is associated with key analogues of depressive symptoms, such as increased floating during forced swimming and decreased exploration of novelty. On the other hand, increased anxiety, altered locomotor activity, and loss of body weight were consequences of chronic stress, which occurred independently from anhedonia. Thus, behavioral correlates of stress-induced anhedonia and of chronic stress alone can be separated in the present model.

CENTRAL NERVOUS SYSTEM (CNS)
- Ischemic Strokes -
Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke. (2009)
Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke.
N. Blondeau, C. Nguemeni, D. N. Debruyne, M. Piens, X. Wu et al.
Institut de Pharmacologie Moléculaires et Cellulaires - UMR6097, C.N.R.S, Cerebrovascular Pathologies and Therapeutic Laboratory, Valbonne, France ; University of Nice Sophia Antipolis, Department of Neuroscience, Nice, France.
Published in "Neuropsychopharmacology" (2009-11-30)

Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicle-treated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24_h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia.

- Epilepsy -
CNS Disorders—Current Treatment Options and the Prospects for Advanced Therapies. (2008)
CNS Disorders—Current Treatment Options and the Prospects for Advanced Therapies.
J. C. DiNunzio, R. O. WilliamsIII.
The University of Texas at Austin, Division of Pharmaceutics, Austin, USA.
Published in "Drug Development and Industrial Pharmacy" (2008-11-01)

The development of new pharmaceutical products has successfully addressed a multitude of disease states; however, new product development for treating disorders of the central nervous system (CNS) has lagged behind other therapeutic areas. This is due to several factors including the complexity of the diseases and the lack of technologies for delivery through the blood–brain barrier (BBB). This article examines the current state of six major CNS disease states: depression, epilepsy, multiple sclerosis (MS), neurodegenerative diseases (specifically Alzheimer's disease [AD]), neuropathic pain, and schizophrenia. Discussion topics include analysis of the biological mechanisms underlying each disease, currently approved products, and available animal models for development of new therapeutic agents. Analysis of currently approved therapies shows that all products depend on the molecular properties of the drug or prodrug to penetrate the BBB. Novel technologies, capable of enhancing BBB permeation, are also discussed relative to improving CNS therapies for these disease states.

NEURODEGENERATION
- Parkinson disease -
Pramipexole is active in depression tests and modulates monoaminergic transmission, but not brain levels of BDNF in mice. (2012)
Pramipexole is active in depression tests and modulates monoaminergic transmission, but not brain levels of BDNF in mice.
O. Schulte-Herbrüggen, M. Vogt, H. Hörtnagl, P. Gass, R. Hellweg.
Charité-University Medicine Berlin, Department of Psychiatry and Psychotherapy, Berlin, Germany.
Published in "European Journal of Pharmacology" (2012-02-29)

The dopamine D(2)/D(3) receptor agonist pramipexole exerts antidepressive capacities in patients with Parkinson's disease with little evidence for patients with affective diseases only. Little is known about the neurobiological basis of these antidepressive effects. In this study, C57BL/6N mice received acute or chronic (3 weeks) treatment with pramipexole in different dosages (0.1, 0.3, 1, and 3mg/kg b.w.) and imipramine or saline serving as positive and negative controls. To characterize antidepressant-like effects mice underwent behavioral characterization. In a second experiment dosages of pramipexole shown to be effective were used and candidate brain regions including hippocampus, frontal cortex and striatum were analyzed for levels of 5-hydroxytryptamine (5-HT), noradrenaline and dopamine and their metabolites as well as brain-derived neurotrophic factor (BDNF) to investigate possible neurochemical correlates of behavioral changes. Whereas acute treatment with pramipexole resulted in antidepressive-like effects in the Porsolt Forced Swim Test, Novel Cage Test, Openfield Test and Dark-light-Box Test and a tendency but insignificant effect in the Tail Suspension Test, chronic treatment did not show significant effects in any of the behavioral analyses. Neurochemical analyses revealed a highly significant effect on dopaminergic metabolites in the striatum as well as a moderate transient modulation of the serotonergic system in the hippocampus. BDNF levels were not affected by any dosage and treatment regime in any brain region investigated. In conclusion, the present data substantiate antidepressive effects of pramipexole and indicate a contribution of the dopaminergic and serotonergic metabolism in these effects, but argue against an eminent role of BDNF.

- Alzheimer disease -
CNS Disorders—Current Treatment Options and the Prospects for Advanced Therapies. (2008)
CNS Disorders—Current Treatment Options and the Prospects for Advanced Therapies.
J. C. DiNunzio, R. O. WilliamsIII.
The University of Texas at Austin, Division of Pharmaceutics, Austin, USA.
Published in "Drug Development and Industrial Pharmacy" (2008-11-01)

The development of new pharmaceutical products has successfully addressed a multitude of disease states; however, new product development for treating disorders of the central nervous system (CNS) has lagged behind other therapeutic areas. This is due to several factors including the complexity of the diseases and the lack of technologies for delivery through the blood–brain barrier (BBB). This article examines the current state of six major CNS disease states: depression, epilepsy, multiple sclerosis (MS), neurodegenerative diseases (specifically Alzheimer's disease [AD]), neuropathic pain, and schizophrenia. Discussion topics include analysis of the biological mechanisms underlying each disease, currently approved products, and available animal models for development of new therapeutic agents. Analysis of currently approved therapies shows that all products depend on the molecular properties of the drug or prodrug to penetrate the BBB. Novel technologies, capable of enhancing BBB permeation, are also discussed relative to improving CNS therapies for these disease states.



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Number of animals 1-3 mice if one set of cages is used
1-6 mice if 2 sets of cages are used
Hardware Black and white PVC
Power 110-230 Volts- 9 volts DC
Dimensions 50 x 15 x 30 cm for a set of three cages
Acquisition sampling rate 200 Hz for the sensors
15 images/second for the camera
Analysis Ultra fast even with batches of mice
Parameters measured include immobility time,
motion time, energy and power in motion
PC Requirements OS: Windows 7 / 8, 32 64 bits
CPU: Intel Core i3, 2.4GHz or equivalent
RAM: 3Go
USB: USB 2 / USB 3
Display resolution: 1152x768 pixels
1 free USB port / cage set + 1 free USB port for the camera
Compatible with touch-screen tablet using W8

Model:
BIO-TST4
Tail Suspension Test - Reinvented (Modif.)
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