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PASSIVE AVOIDANCE
(Model: LE870 - for rats)
Fear-motivated tests classically used to assess short-term or long-term memory on small laboratory animals

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! NEW RESEARCH WORK ! A recent publication by M Lachaux, M Souli in "Endochrinology, Diabetes and Metabolism" highlights the merits of using Bioseb's Passive avoidance: Short_and long_term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome

Short_and long_term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome
M Lachaux, M Souli
INSERM U1096, UFR de Sant
Published in "Endochrinology, Diabetes and Metabolism" (2020-04-16)


IntroductionImeglimin, a glucose_lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome_related left ventricular (LV) and vascular dysfunctions.
Methods We used Zucker fa/fa rats to assess the effects on LV function, LV tissue perfusion, LV oxidative stress and vascular function induced by imeglimin administered orally for 9 or 90 days at a dose of 150 mg/kg twice daily.
Results Compared to untreated animals, 9_ and 90_day imeglimin treatment decreased LV end_diastolic pressure and LV end_diastolic pressure_volume relation, increased LV tissue perfusion and decreased LV ROS production. Simultaneously, imeglimin restored acetylcholine_mediated coronary relaxation and mesenteric flow_mediated dilation. One hour after imeglimin administration, when glucose plasma levels were not yet modified, imeglimin reduced LV mitochondrial ROS production and improved LV function. Ninety_day imeglimin treatment reduced related LV and kidney fibrosis and improved kidney function.
Conclusion In a rat model, mimicking Human metabolic syndrome, imeglimin immediately countered metabolic syndrome_related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion and after 90_day treatment myocardial and kidney structure, effects that are, at least in part, independent from glucose control.

Presentation

The inhibition of innate or learned behaviour by association with aversive stimulation has shown to be a very useful tool for researchers working in very different fields. From the study of the interference of drug treatments on a simple learning model to the study of the physiological mechanisms beneath learning or memory, passive avoidance reflexes studies have been used.

Many models have been proposed for these studies. However, among those most widely used, that suggested by Kurtz & Pearl in 1960 (J. Comp Physiol. Phycol. 53:201-6) and later modified by Bures & Buresova (J. Comp. Physiol. Phycol. 56:268-62, 1963) is proven. In this model, sometimes called ‘One-trial learning’, ‘Two-compartment test’ or ‘Memory test’ it is intended to inhibit, by aversive stimulus, the rodents tendency to abandon large, open and brightly illuminated spaces so as to hide in small dark ones.


Operating principle

The model has a set of variables of easy determination and control (i.e. entrance to the small compartment latency), offering, at the same time, an ample parameters spectrum whose effect can be studied (v. gr. the interval between the aversive stimulation and the retention test).

Passive Avoidance studies can be carried out by means of an experimental chamber that comprised of two differently sized enclosures, a big white one and a small black one, according to the original design.


Passive avoidance complete system with LE2708 Avoidance programmer
Passive avoidance complete system with LE2708 Avoidance programmer



In this experimental chamber, the animal’s position is detected by using weight gauges. This system, which uses high sensitivity weight transducers that range from 10 to 800 grams, provides more effective and reliable detection of animal responses (zones entries) than systems based on photocells beams or on grid floor displacements.


Options

BIOSEB Passive Avoidance boxes may be controlled either through LE2708 Programmer or SHUTAVOID software.
The first option is recommended for one single box set-ups, and may be combined with SEDACOM software - which is limited to enable data transfer from the programmer to a PC through a RS232 port. It is not necessary the interface neither the use of board installed into the PC. The link is carried out by one only cable from one Box to the other. The first Box is connected to PC or Laptop by the port RS 232 or USB.
The second option is suitable for controlling a number of boxes simultaneously.


Click here to download PDF data with detailled information about our Passive Avoidance test

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

MOTOR CONTROL
- Locomotion -
Association between arthritis score at the onset of the disease and long-term locomotor outcome in adjuvant-induced arthritis in rats (2015)
Association between arthritis score at the onset of the disease and long-term locomotor outcome in adjuvant-induced arthritis in rats
Mossiat C, Laroche D, Prati C, Pozzo T, Demougeot C, Marie C
INSERM U1093, University Bourgogne Franche-Comté, Dijon, France.
Published in "Arthritis Res Ther." (2015-07-17)

INTRODUCTION:
To investigate the connection between the intensity of initial symptoms of inflammation and locomotor outcome in rheumatoid arthritis, we examined the relationship between long-term locomotor abnormalities and signs of inflammation at the onset of the disease in adjuvant-induced arthritis (AIA) in rats.

METHODS:
The arthritis score and hind-paw diameter were followed from immunization to day 195 (~7 months). At this time, locomotion was recorded during forced treadmill walking using 3D motion technology before radiographic scoring of hind limb joint damage. Many locomotor parameters were analyzed including time and length parameters, limbs kinematics, lateral paw position at toe off, maximal hind-paw elevation and posture. Ankle mobility was assessed from range of motion (ROM) of the joint during locomotion. Experiments were run in AIA (n = 18) and age-matched non-AIA rats (n = 8).

RESULTS:
All AIA rats exhibited signs of inflammation at day 14 with a peak of inflammatory symptoms at day 22 post-immunization. After the first episode of inflammation, 83 % of AIA rats demonstrated recurrent disease (from week 6 to week 23). The frequency of inflammatory episodes (1 to 5) was not linked to the arthritis score at day 22. At day 195 post-immunization, AIA rats showed significantly impaired locomotion and radiographic lesions as compared to control rats. Significant relationships were observed between most locomotion-related parameters and concurrent ROM of ankle, which correlated negatively with the radiographic score. ROM of ankle at day 195 correlated negatively with both the arthritis score and hind-paw diameter measured at day 14, 22 and 30 post-immunization.

CONCLUSION:
Decreased ankle mobility can be considered a driver of locomotion impairment in AIA. In this model, the severity of the initial inflammatory symptoms had a good prognostic value for long-term locomotor outcome.

Kinematics of obstacle clearance in the rat. (2011)
Kinematics of obstacle clearance in the rat.
O. Perrot, D. Laroche, T. Pozzo, C. Marie.
INSERM, U887, Motricité-Plasticité, Dijon, France.
Published in "Behavioural Brain Research" (2011-10-31)

Although the rat has become the favourite animal model in preclinical research on locomotion, studies designed to assess the strategy used by rats to avoid obstacle are lacking. Using an optoelectronic 3D motion analysis system, we therefore, compared the step pattern, timing and length variables of locomotor cycles, trajectories and joint angles of limbs when rats step between and over obstacles (3 cm-high) fixed on a treadmill belt (25 cm/s). Motion in all four limbs of adult animals with an initial age of 11 weeks was serially recorded for a period of 10 weeks. The results showed that obstacle clearance is associated with the reorganization of the basic step pattern resulting in increased stride length of all limbs, increased duration of the swing phase of the hindlimbs only, and the appearance of two quadrupedal stance phases. They also revealed that the elevation of limbs above the obstacle not only involves flexion but also displacement of the corresponding girdles. Remarkably, the trajectory of the trailing forelimb to get over the obstacle is almost a mirror image of the trajectory of the leading forelimb. Lastly, all of the parameters measured remained stable over the observation period during which body weight gain reached 100g (one third of the initial body weight). In conclusion, our study may provide a basis for future studies aimed at understanding the neural pathways involved in pathologies associated with deficit/recovery of challenged locomotion in rats.

OTHER DISORDERS
- Cognitive performance -
Multifunctional 6-fluoro-3-[3-(pyrrolidin-1-yl)propyl]-1,2-benzoxazoles targeting behavioral and psychological symptoms of dementia (BPSD) (2020)
Multifunctional 6-fluoro-3-[3-(pyrrolidin-1-yl)propyl]-1,2-benzoxazoles targeting behavioral and psychological symptoms of dementia (BPSD)
A Bucki, M Marcinkowska, J _niecikowska, A Zagórska et al
Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Published in "European Journal of Medicinal Chemistry" (2020-02-18)

Patients suffering from dementia experience cognitive deficits and 90% of them show non-cognitive behavioral and psychological symptoms of dementia (BPSD). The spectrum of BPSD includes agitation, depression, anxiety and psychosis. Antipsychotics, e.g. quetiapine, have been commonly used off-label to control the burdensome symptoms, though they cause serious side effects and further cognitive impairment. Therefore, the development of targeted therapy for BPSD, suitable for elderly patients, remains relevant.
A multitarget-directed ligand, acting on serotonin 5-HT2A and dopamine D2 receptors (R) and thus exerting anti-aggressive and antipsychotic activity, as well as on 5-HT6Rs and 5-HT7Rs (potential pro-cognitive, antidepressant and anxiolytic activity), poses a promising strategy for the treatment of BPSD. Antitargeting muscarinic M3R and hERG channel is expected to reduce the risk of side effects. We obtained a series of stereoisomeric compounds by combining 6-fluoro-1,2-benzoxazole moiety and arylsulfonamide fragment through pyrrolidin-1-yl-propyl linker.
N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide showed a substantial affinity for the targets of interest (pKi = 8.32–9.35) and no significant interaction with the antitargets. Functional studies revealed its antagonist efficacy (pKB = 7.41–9.03). The lead compound showed a promising profile of antipsychotic-like activity in amphetamine- and MK-801-induced hyperlocomotion (MED = 2.5 mg/kg), antidepressant-like, as well as anxiolytic-like activity in mice (MED = 0.312 and 1.25 mg/kg in the forced swim and four-plate tests, respectively). Notably, the novel compound didn’t affect spontaneous locomotor activity, nor induced catalepsy or memory deficits (step-through passive avoidance test) in therapeutically relevant doses, which proved its benign safety profile. The overall pharmacological characteristics of the lead compound outperformed the reference drug quetiapine, making it a promising option for evaluation in the treatment of BPSD.

MUSCULAR SYSTEM
- General muscular system -
The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance (2017)
The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance
A Dayal, K Schrötter, Y Pan, K Föhr, W Melzer, M Grabner
Medical University of Innsbruck, Austria
Published in "Nature Communications" (2017-09-07)

Skeletal muscle excitation?contraction (EC) coupling is initiated by sarcolemmal depolarization, which is translated into a conformational change of the dihydropyridine receptor (DHPR), which in turn activates sarcoplasmic reticulum (SR) Ca2+ release to trigger muscle contraction. During EC coupling, the mammalian DHPR embraces functional duality, as voltage sensor and l-type Ca2+ channel. Although its unique role as voltage sensor for conformational EC coupling is firmly established, the conventional function as Ca2+ channel is still enigmatic. Here we show that Ca2+ influx via DHPR is not necessary for muscle performance by generating a knock-in mouse where DHPR-mediated Ca2+ influx is eliminated. Homozygous knock-in mice display SR Ca2+ release, locomotor activity, motor coordination, muscle strength and susceptibility to fatigue comparable to wild-type controls, without any compensatory regulation of multiple key proteins of the EC coupling machinery and Ca2+ homeostasis. These findings support the hypothesis that the DHPR-mediated Ca2+ influx in mammalian skeletal muscle is an evolutionary remnant.

- Skeletal functions -
The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance (2017)
The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance
A Dayal, K Schrötter, Y Pan, K Föhr, W Melzer, M Grabner
Medical University of Innsbruck, Austria
Published in "Nature Communications" (2017-09-07)

Skeletal muscle excitation?contraction (EC) coupling is initiated by sarcolemmal depolarization, which is translated into a conformational change of the dihydropyridine receptor (DHPR), which in turn activates sarcoplasmic reticulum (SR) Ca2+ release to trigger muscle contraction. During EC coupling, the mammalian DHPR embraces functional duality, as voltage sensor and l-type Ca2+ channel. Although its unique role as voltage sensor for conformational EC coupling is firmly established, the conventional function as Ca2+ channel is still enigmatic. Here we show that Ca2+ influx via DHPR is not necessary for muscle performance by generating a knock-in mouse where DHPR-mediated Ca2+ influx is eliminated. Homozygous knock-in mice display SR Ca2+ release, locomotor activity, motor coordination, muscle strength and susceptibility to fatigue comparable to wild-type controls, without any compensatory regulation of multiple key proteins of the EC coupling machinery and Ca2+ homeostasis. These findings support the hypothesis that the DHPR-mediated Ca2+ influx in mammalian skeletal muscle is an evolutionary remnant.

Mitochondria of trained skeletal muscle are protected from deleterious effects of statins. (2012)
Mitochondria of trained skeletal muscle are protected from deleterious effects of statins.
J. Bouitbir, F. Daussin, A.-L. Charles, L. Rasseneur, S. Dufour et al.
CHRU of Strasbourg, Physiology and Functional Explorations Department, Strasbourg, France
Published in "Muscle and Nerve" (2012-01-13)

Introduction: Statins are associated with adverse skeletal muscle effects. Our objective was to determine if muscular adaptations following exercise training prevented deleterious effects of atorvastatin in glycolytic skeletal muscle. Methods: 20 rats were divided into 2 groups: a control group (n=10; Cont) and a 10 days of training group (n=10; Training). Using the permeabilized fibers technique, we explored mitochondrial function. Results: Exercise training increased Vmax and H2O2 production without altering the free radical leak, and mRNA expression of SOD2 and Cox1 were higher in trained muscle. In the Cont group, atorvastatin exposure increased H2O2 production and decreased skeletal muscle Vmax. The decreased Vmax effect of atorvastatin was dose dependent. Interestingly, the half-maximal inhibitory concentration (IC50) was higher in the Training group. H2O2 production increased in trained muscle after atorvastatin exposure. Conclusions: These results suggest that improvements in mitochondrial respiratory and antioxidant capacities following endurance training protected them against statin exposure.



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Mouse box dimensions 250 (W) x 250 (D) x 240 (H) mm White compartment and
195 x 108 x 120 mm Black compartment
Rat box dimensions 310 (W) x 310 (D) x 240 (H) mm White compartment and
195 x 108 x 120 mm Black compartment
Minimum weight detected 10 grams (Mouse Box) and 40 grams (Rat Box)
Material Composition Methacrylate, aluminium, stainless steel
Maximum number of stations 8 stations connected to a PC
Connection of several units
to PC
Neither PC interface nor PC card are required. One cable connects all units to the PC.
Certifications CE Compliant
Power Supply 110V/220V, 50/60Hz

Model:
LE870
Passive avoidance
for rats Contact us

Related products:
LE872
Passive avoidance
for mice Contact us
LE916
Shuttle Boxes
for rats Contact us
LE918
Shuttle Boxes
for mice Contact us

Accessories :
SHUTAVOID
SHUTAVOID software
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