WO2010089220A1

WO2010089220A1 - Cage with an enriched environment for housing rodents

Info

Publication number: WO2010089220A1
Application number: PCT/EP2010/050811
Authority: WO
Inventors: Laurent Bezin; Marion Moreau; Raafat Fares
Original assignee: Laurent Bezin; Marion Moreau; Raafat Fares
Priority date: 2009-02-09
Filing date: 2010-01-25
Publication date: 2010-08-12
Also published as: FR2941844A1; FR2941844B1

Abstract

The invention relates to cage (1) for rodents, including: a feeding area (3); a drinking area; a loop circuit including first and second passageways to be travelled through by a rodent, each of said passageways connecting the feeding area with the drinking area, the first passageway (4) being able to be passed through in only one direction; and a maze (2) arranged in the second passageway.

Description

ACCOMMODATION CAGE FOR RODENTS WITH ENRICHED ENVIRONMENT

The invention relates to rodent accommodation cages, such as cages used in animal experiments, particularly with rats or mice.

The cages currently used for animal testing are designed to meet the standardization of rodent housing procedures. The standardization of the living environment is necessary to conduct reproductive experiments on rodents. However, this standardization results in cages considerably depleting the environment in which the animal evolves, imposing a hierarchical subordination relationship and preventing it from expressing certain behaviors essential to its species such as straightening, playing, or stimulating the animals. physical activities, exploratory and mnemic, solicited during the search for food and drink, essential for its survival. This impoverishment leads to the modification of many physiological functions, in particular those associated with stress management, metabolism and cognitive abilities. This is detrimental to the welfare of the animal, which is a requirement for conducting good quality scientific experiments. In addition, animal testing is receiving increasing public attention as the public becomes more and more sensitive to the quality of life of laboratory animals. The conditions of accommodation in such cages are thus decried by the public. To increase the physiological well-being of the animal, it is known to enrich the living environment of the rodent by incorporating in the cage toys, actimetry wheels or tunnels. Enrichment usually involves objects that change in size, shape, composition, texture and smell. Enrichment also involves the solicitation of voluntary motor activities. During the enrichment procedure, it is essential to bring complexity to the environment, with processes stimulating olfactory, visual and somatosensory functions, as well as novelty. In practice, there is an increase in brain robustness and regenerative capacity in adult rodents in enriched living environments. In particular, there is an increase in the expression of the gene encoding neurotrophic factor derived from the brain (BDNF) in the hippocampus and an increase in neurogenesis (renewal of neuronal populations) in the hippocampus. An enriched living environment makes it easier to highlight the recovery and regeneration abilities of rodents as a result of brain damage. However, the establishment of such means of enrichment of the living environment is based on

SUBSTITUTE SHEET (RULE 26) empirical experience and transforms the living environment in relation to the prescribed standardization conditions. Enrichment protocols are also poorly described to be reproducible. Enrichment protocols are therefore much too subjective to lead to satisfactory experimental conditions, that is to say standardized.

Whether in a traditional standard setting, or sometimes even in an empirically enriched environment, the accommodations do not allow animals, many of them in the cage, to escape the social hierarchy, particularly that imposed by dominant males. Furthermore, in empirically enriched media, it is impossible to determine whether all animals were subjected similarly to enrichment procedures.

There is therefore a need for rodent housing cages both to enrich their living environment and to define standardized living conditions. The invention aims to solve one or more of these disadvantages.

The invention thus relates to a cage for rodents, comprising: a food zone; -a drinking area;

a loop circuit comprising first and second passages intended to be traversed by a rodent, said passages each joining the food zone with the drinking zone, the first passage being able to be traversed only in one direction; a labyrinth arranged in the second passage.

According to a variant, the cage comprises a first stage in which the food zone, the drinking zone and the first passage are arranged, and a second stage in which the labyrinth and the second passage are arranged.

According to another variant, the cage comprises a chute having an inlet disposed near an outlet of the labyrinth and an outlet opening into the food zone.

According to another variant, the labyrinth is removably mounted in the second passage.

According to yet another variant, the labyrinth has black and / or opaque walls. According to one variant, the labyrinth has two inputs and two outputs.

According to another variant, the first passage comprises a swing door movable between an open position and a closed position, and a return member urging the swing door to its closed position.

According to another variant, the food zone comprises a feeder and in which the drinking zone comprises a liquid dispenser. According to yet another variant, the beverage zone comprises an exercise wheel and a housing having at least two inlet ports disposed at opposite ends of the housing.

Other characteristics and advantages of the invention will emerge clearly from the description which is given hereinafter, by way of indication and in no way limitative, with reference to the appended drawings, in which:

FIG 1 is a front sectional view of a cage according to one embodiment of the invention; FIG 2 is a sectional view from above of the cage of Figure 1 in its upper part;

FIG 3 is a sectional view from above of the cage of Figure 1 in its lower part;

FIG 4 is a front view of the front wall of the cage of Figure 1; FIG. 5 is a side view of the front wall;

FIG 6 is a side view of a side wall of the cage; FIGS. 7 to 12 are diagrammatic representations of various interchangeable labyrinths that can be mounted in the cage;

FIG 13 is a schematic representation of a housing cage for rodents before weaning;

FIGS. 14 to 16 are plan views of sheets transformed to form the cage of FIG. 13.

The invention provides a rodent cage comprising a food zone and a beverage zone. A loop circuit is formed in the cage and has two passages intended to be traversed by a rodent. These passages each join the food zone to the drinks zone. The first pass can only be crossed in one direction. In addition, a labyrinth is located in the second passage. After drinking, a rodent wishing to feed will necessarily have to cross the labyrinth (or the opposite depending on the direction of passage allowed by the first pass). This will ensure that rodents all travel a minimum distance to meet their biological needs, regardless of the hierarchical relationship between them. In addition, rodents will regularly exercise their sense of direction inside the labyrinth. Thus, the results of experiments conducted on such rodents may be much more significant and less sensitive to differences in behavior between rodents.

Figures 1 to 3 are sectional views showing a cage 1 according to one embodiment of the invention. In the example shown, cage 1 is parallelepipedic shape. The cage comprises a bottom wall 1 1, front and rear walls 16 and 17, side walls 14 and 15, a cover wall 13 and an upper floor wall 12. A wall 18 extends to the floor between the walls 11, 12, 16 and 17. The wall 18 separates a food zone and a drinking zone formed on the wall January 1. The wall 18 has orifices closed by doors 4. These doors 4 form a one-way passage between the food zone and the beverage zone. Rodents can only cross the food zone to the drink zone, but not the other way around. Feeders 3 are disposed within the food zone. Water tanks 6 are contiguous to the wall 16 and have nipples 61 accessible within the drinking zone. The wall 12 delimits an upper stage inside the cage 1. The rodents can move between the upper stage and the lower stage via a ramp 92 and via a toboggan 91. The ramp 92 and the slide 91 are disposed at opposite axial ends of the cage 1. Ramp 92 is accessible for rodents present in the drinking zone. The toboggan 91 opens into the food zone. A labyrinth 2 is provided on the upper floor of the cage 1. The labyrinth 2 covers the passage of the upper floor between the ramp 92 and the slide 91. As a result, a rodent wishing to move from ramp 92 to slide 91 on the upper level is forced to cross labyrinth 2.

A circuit is thus formed inside the cage 1. This circuit passes through the food zone, the drinking zone and the labyrinth 2. The gates 4 form one-way passages from the food zone to the drinking zone. The labyrinth 2 forms a passage from the drink zone to the food zone.

When a rodent is present in the drinking zone, he can not return to the feeders 3 through the doors 4 to feed. Therefore, he must first climb the ramp 92, cross the labyrinth 2, then down the slide 91. An exercise is thus imposed on the rodent to ensure his livelihood. The enrichment of the different rodents will therefore be relatively equitable. In addition, his sense of direction is put to the test inside labyrinth 2, which requires his cognitive functions.

The doors 4 may be rotatably mounted relative to the wall by means of a hinge 5. The stroke of a door 4 may extend between a closed position where it abuts against the wall 18 and a position open where it is tipped towards the inside of the drink area. A return member may urge the doors 4 to their closed position. Advantageously, the living environment of rodents is enriched. In this case, games are arranged inside the beverage area. Three Exercise wheels 93 are thus fixed to the wall 17 and disposed in the drinking zone. In addition, a housing 94, in which a tunnel is formed, is disposed in the middle part of the drinking zone. Due to the presence of these games, rodents will spend most of their time in this area. The walls 11 to 17 may for example be made in plexiglass plates having a thickness of approximately 2 mm. One or more of the walls 11 to 17 will advantageously be transparent, so that the activity in the cage 1 can be followed continuously, for example by means of cameras. Infrared cameras can be used to observe the activity of rodents in the dark. The walls 11 and 14 to 17 may be secured by gluing, for example using a cyanoacrylate type glue. The walls 12, 13 and 18 are advantageously removable to facilitate interventions inside the cage 1. The wall 12 rests on stops 96 fixed on the walls 14 to 17 and protruding towards the inside of the cage. These stops 96 can be fixed by gluing.

Otherwise, it is also conceivable that the wall 12 slides through a slot made in the wall 16, while bearing on the wall 18, to come at the end of the race fit into a notch made in the inner face of the wall 17. In this case, a 90 ° downward return will be provided in the wall 12 and will be wedged against the wall 16 at the end of the stroke.

The walls 14 and 15 are provided with gripping handles 95, making it possible to easily move the cage 1.

The wall 11 has orifices 97. These orifices 97 make it possible to evacuate water during a cleaning of the cage 1. In the example illustrated, the wall 15 is provided with orifices 99 allowing an air inlet. inside the cage 1. Other walls may also be provided with such openings.

Rodents may be equipped with electronic chips to identify them. Such electronic chips can be placed under the skin of each rodent. Rodents can be located by different sensors placed inside the cage. The information collected by the sensors will make it possible, for example, to determine the distance traveled by the rats or their travel habits.

Advantageously, the slide 91 is made with a shape steep enough to prevent a rodent to go back to the upper floor. The slide 91 and the ramp 92 may be respectively secured to the walls 14 and 15, or to the wall 12, or may be removably mounted between stops to facilitate their cleaning.

For a cage 1 intended for rats, the surface of the wall 11 will advantageously be of the order of 0.5 m ² . By cumulating the floor area of the walls 11 and 12, the cage 1 can thus have a floor area for rats of approximately 0.9 m ² . The wall 11 may for example be of shape rectangular and have a length of 0.8 m by 0.6 m. With such a surface, the number of rats can be increased. One can consider placing a dozen rats in cage 1 to increase social interaction between rats and to offer a greater number of fun activities. For a dozen rats, it is advantageous to have at least three feeders 3 is at least three teats 61, to limit the development of territorial characters.

The exercise wheels 93 may be made of plastic, or preferably metal to limit their degradation. The wheels 93 may be equipped with a counting mechanism of turns and a rodent detector present. The activity of each rat equipped with an electronic chip can thus be studied. The detector may limit the use of the wheel 93 to a single rodent simultaneously, for example by blocking the rotation of the wheel when rodents are simultaneously present in the wheel 93. The detector may also issue a reward rodent when a certain number of laps will have been made. Thus, physical efforts will be encouraged but not imposed, which reduces the stress of the rodent. The number of turns to be made to obtain a reward may change over time for each rodent.

The housing 94 forms a tunnel on which several inlet ports open. The housing 94 is advantageously raised with respect to the wall 11 by feet. These feet can fit into the wall 11, or it is also possible to maintain them in position by means of magnets. The housing 94 may advantageously be formed in a material that is transparent to humans but opaque for the vision of rodents. The housing 94 may for example be made of translucent red plastic materials, which are opaque for the vision of rats. The housing 94 will advantageously have at least four openings opening into the tunnel. Thus, the development of aggressive characters due to the solicitation of territorial instincts is mitigated, the rodents can borrow different orifices.

The labyrinth 2 can be made in one piece by molding. Cage 1 can also be used in domestic applications to receive rodents as pets. In such a case, the labyrinth may advantageously be formed of modular removable walls, so that the user can freely redefine the paths that the rodent will have to take to cross the labyrinth.

Although there are illustrated feeders 3 disposed within the cage 1, the cage 1 may advantageously have lateral orifices through which the feeders 3 are introduced into the cage. Thus, the filling and cleaning of the feeders 3 will be facilitated. The invention also proposes a procedure for standardizing the revolution of the living environment formed by the cage. According to this procedure, labyrinth 2 is changed at regular intervals. For this purpose it will be possible to use 6 different interchangeable labyrinths, such as those illustrated in FIGS. 7 to 12. The labyrinths may be held in position axially by means of wedges 98 protruding from the wall 12. The labyrinths will be changed in a precise order, for example every other day, or Monday, Wednesday and Friday. When the six labyrinths have been used, these six labyrinths can be used in the same order but by turning them so that the face that was near the ramp 92 is found near the slide 91. Thus, rodents have 12 variants of path through labyrinths 2. In order to ensure standardization, the same labyrinths can be used and changed in the same order for all the experiments carried out in enriched medium. This procedure allows to renew the novelty stimulus and associated cognitive activities (exploration by smell, recovery and spatial learning) in a reproducible and standardized order. Labyrinth changes force the use of rodent orientation by regularly removing olfactory landmarks.

These labyrinths 2 advantageously have two inputs and two outputs to mitigate the development of aggressive characters between rodents. The routes to follow differ for these two entries. These labyrinths will advantageously have a height sufficient to allow the recovery of rodents during their exploratory behavior. The cage 1 may also have a greater number of wheels 93 to reduce the development of aggressive characters.

This standardization procedure makes it possible to reproducibly enrich the living environment in order to stimulate, by non-invasive and physiological means, the cerebral robustness capacities of rodents. Two molecules play a key role in increasing brain robustness: brain-derived neurotrophic factor (BDNF) and erythropoietin (Epo). The inventors have already demonstrated that the repetition of severe and short-lived hypoxia induces the expression of Epo and its receptor in the most vulnerable regions of the brain. The inventors have also demonstrated that enriched housing (from weaning to adulthood) can induce as effectively as hypoxia the expression of Epo and / or its receptor in these regions. vulnerable, thereby increasing the likelihood of responding favorably to Epo's neuroprotective The intrinsic neuroprotective capacities of the central nervous system therefore depend on the hosting conditions, and are optimal when the enrichment allows the development of specific behaviors. Demonstration of the impact of the animal's psycho-social environment on cerebral gene expression is of major importance in all neuropharmacology studies.

According to some experimental protocols, rats are provided at age 14 days with a foster mother. At the age of 21 days, they are separated from their mothers and will be randomly distributed in cages 1. FIG. 13 represents an accommodation cage 7 (having the dimensions of a labyrinth 2) intended to receive baby rodents and their foster mothers. This accommodation cage 7 is intended to facilitate the acclimation of the rats to a cage 1 provided with a labyrinth 2. This cage 7 may be placed in place of the labyrinth 2 in the cage 1 during the weaning period. The cage 7 has niches 71 to 74 each arranged in a corner and intended to house the babies and their foster mother. The niches 71 and 74 open in a median zone 75. The median zone 75 has walls 76 and 77 forming obstacles to the movement of rodents. A trough 3 is disposed between the niches 72 and 74. A trough 6 provided with a nipple 61 is disposed between the niches 71 and 73. At the time of weaning, the babies will be forced to leave their niche and to cross the median zone 75 to feed and drink. This constitutes for them a step before discovering the labyrinth 2 when they are released in the cage 1.

The cage 7 can be assembled by cutting and folding several sheets, illustrated in FIGS. 14 to 16. In these figures, the solid lines correspond to cutting lines, the dashed lines correspond to fold lines. The sheet 8 is intended to form a base of the cage 7. The flaps 82 are thus bent at 90 ° with respect to a median portion 81. The sheet 9 is intended to form the median zone 75. The sheet 9 comprises a median portion 78 and flaps 79 to be folded at 90 ° with respect to this middle portion 78. The walls 76 and 77 are formed in the middle portion 78 by folding at 90 ° precut tabs. The sheet 10 is intended to be cut into four strips. The strips obtained then undergo several bending at 90 ° to form respectively niches 71 to 74.

Claims

1. Cage (1) for rodents, characterized in that it comprises: - a food zone (3); -a drinking area;

a loop circuit comprising first and second passages intended to be traversed by a rodent, said passages each joining the food zone with the beverage zone, the first passage (4) being traversable only in one direction; a labyrinth (2) disposed in the second passage.

The cage (1) for rodents according to claim 1, comprising a first stage in which the food zone, the drinking zone and the first passage (4) are arranged, and a second stage in which the labyrinth (2) and the second pass are arranged.

The rodent cage of claim 2 comprising a chute (91) having an inlet disposed proximate an outlet of the labyrinth and an outlet opening into the food zone.

A rodent cage according to any one of the preceding claims, wherein the labyrinth (2) is removably mounted in the second passage.

5. Rodent cage according to any one of the preceding claims, wherein the labyrinth (2) has black and / or opaque walls.

Rod cage according to any one of the preceding claims, wherein the labyrinth (2) has two inlets and two outlets.

7. A rodent cage according to any one of the preceding claims, wherein the first passage comprises a movable flap door (4) between an open position and a closed position, and a return member (5) urging the swing door to its closed position.

A rodent cage according to any one of the preceding claims, wherein the food zone comprises a feeder (3) and wherein the drinking zone comprises a liquid dispenser (6, 61).

The rodent cage according to any of the preceding claims, wherein the beverage zone comprises an exercise wheel (93) and a housing (94) having at least two inlet ports disposed at opposite ends. of the case.