JP2009261365A - System for measuring stimulus response, and method for measuring stimulus response - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To achieve quantitative evaluation of depressive states of animals. <P>SOLUTION: A stimulus is provided for an animal 200 to be measured with a stimulation bar 13 to detect a load (force) applied to the stimulation bar 13 with a load sensor 14 based on behavior exhibited for the stimulation bar 13 by the animal 200 to be measured. The amount of response of the animal 200 to be measured to the stimulus for the stimulation bar 13 is measured by a measuring/commanding apparatus 30 on the basis of the load (force) detected with the load sensor 14. Thus, the depressive state of the animal 200 to be measured can quantitatively be evaluated. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a stimulus response measurement system and a stimulus response measurement method for applying a mechanical stimulus (mechanical stimulus) such as a light contact stimulus to a measurement target animal and measuring a response behavior to the stimulus.

Conventionally, various analysis systems have been proposed as methods for analyzing animal behavior.
For example, Patent Literature 1 and Patent Literature 2 below propose a method of photographing an animal as a model and analyzing the behavior of the animal using the photographed time-series video data.

  However, since Patent Document 1 and Patent Document 2 described above merely observe and analyze the behavior of the animal, the response behavior of the animal to a mechanical stimulus such as a light contact stimulus (coarse tactile pressure sense stimulus) is observed. I couldn't.

JP 2006-75138 A JP 2004-89027 A

  In general, skin sensations to animal stimuli include thermal pain sensations, discriminating tactile sensations, and gross tactile sensations (tactile sensations for mechanical contact, etc.). These sensations are received in the skin by different terminal receptors, relayed by different nerve cells, and transmitted to the cerebral cortical sensory areas by different nerve conduction pathways. Therefore, these three tactile sensations are clearly distinguished as different sensations.

  At present, several measuring devices for analyzing the response of experimental animals to thermal pain sensation are already on the market, and measuring methods using them have been established and various studies are being conducted. On the other hand, behavioral research on response behavior to coarse tactile sensation has not been carried out much. In addition, no research equipment has been developed to measure response behavior to coarse tactile sensation. This is thought to be due to the fact that coarse tactile sensation was clinically less important than thermal pain sensation and discriminating tactile sensation.

  It is considered that the presence or absence of a response to a coarse tactile pressure stimulus is strongly influenced by the state of the emotional center (limbic system), that is, the mental state of the animal. Animals whose emotional centers are not stable, that is, mentally irritated depressed animals, often exhibit hypersensitive response behavior to mechanical stimuli such as gross tactile stimuli (light contact stimuli).

  That is, it is considered that the state of the emotional center of an animal can be inferred by using mechanical stimulation such as coarse tactile pressure sense stimulation (light contact stimulation). However, in the prior art, mechanical stimulus such as coarse tactile pressure sense stimulus was given to the animal to be measured, and the response to the mechanical stimulus could not be measured. could not.

The present invention has been made in view of such problems, and an object of the present invention is to provide a stimulus response measurement system and a stimulus response measurement method that realize quantitative evaluation of an animal's depression.

  Research using experimental animals is indispensable for the development of drugs for depression and stress mental disorders. However, unlike many other diseases, these diseases cannot be diagnosed by blood tests or image diagnosis. Therefore, it is essential to conduct behavioral testing methods and assess therapeutic effects.

  Currently, for screening for depression that has developed in experimental animals, behavioral methods for observing forced swimming tests and male-male attack behavior are being carried out. However, all methods require advanced analysis skills and it is not easy for beginners to obtain reliable findings. Moreover, since the same animal cannot be used for continuous testing, it is difficult to measure the onset and cure of depression over time. Therefore, it is necessary to develop a research instrument that can easily screen depression for beginners and can objectively evaluate the progression and healing of depression.

  As a symptom of mental illness including depression, “psychological symptoms that excessively respond to mild stimuli that would normally be ignored” have been pointed out. It is a psychiatric symptom expressed in words such as “I can't stand anything” or “I am easy to be crisp”.

  In experimental animals given long-term stress, depression often develops. In these animals, behaviors may appear that are hypersensitive to minor mechanical stimuli. For example, when an animal (mouse, rat) that has developed depression is lightly touched with a plastic stick, the action of violently removing the stick with the hind limbs (contact stimulus response action) and the action of biting the stick (objective attack action) remarkably appear. Since these response behaviors are not often observed in normal animals, they are extremely important as an index for detecting depressive symptoms. Therefore, if these can be measured quantitatively, the progression and cure of depression can be expressed numerically.

  Mechanical stimuli such as light contact stimuli are not noxious stimuli such as thermal pain stimuli and do not cause escape reflexes. That is, no spinal reflex is induced. The decision to “escape” or “ignore” from a mechanical stimulus is made by the cerebral neocortex based on the determination of pleasure / discomfort in the emotional center (limbic system) of the animal. If the stimulus is determined to be unpleasant by the animal's emotional center, the cerebral neocortex issues a command to “escape” from the stimulus. If it is determined that the stimulus can be left unattended, the stimulus is ignored.

  In animals with depressive symptoms, the emotional center responds sensitively to minor mechanical stimuli and develops responsive behavior at low thresholds. If an animal with depressive symptoms cannot “escape” from an unpleasant stimulus, an “attack” is applied to the stimulus to try to repel the stimulus.

  Accordingly, the present inventors have focused on these behaviors of animals with depressive symptoms, and invented a measurement method for detecting depressive symptoms and a measurement method for quantitatively evaluating the strength of depressive symptoms. And in order to perform the measurement method simply and objectively with high reliability, the stimulus response measurement system was invented.

  The stimulation response measurement system of the present invention includes a stimulation rod that gives a stimulus to a measurement target animal, and the measurement target animal is applied to the stimulation rod when the stimulation target animal is stimulated by the stimulation rod. Detecting means for detecting a load applied to the stimulation rod based on the action caused to the action, and measuring means for measuring a response amount of the animal to be measured to the stimulation based on the load detected by the detecting means And have.

  The stimulation response measuring method of the present invention includes a stimulation step of applying a stimulus to a measurement target animal using a stimulation rod, and the measurement target animal when the stimulation target rod is stimulated by the stimulation rod. A detection step of detecting a load applied to the stimulus bar based on an action caused to the stimulus bar, and a response amount to the stimulus of the measurement target animal based on the load detected in the detection step Measuring step.

  ADVANTAGE OF THE INVENTION According to this invention, the depression state of a to-be-measured animal can be evaluated quantitatively.

  Embodiments of the present invention will be described below with reference to the accompanying drawings.

FIG. 1 is a photograph showing an example of the appearance of a stimulus response measurement system 100 according to an embodiment of the present invention.
As shown in FIG. 1, the stimulus response measurement system 100 of this embodiment includes an animal stimulus / stimulus response detection device 10, a stimulus control device 20, and an analog / digital converter (A / D converter). A command device 30, a display device 40, and an operation input device 50 are included.

  The animal stimulation / stimulus response detection apparatus 10 accommodates a measurement target animal, applies a mechanical stimulus to the measurement target animal using a stimulation rod, and the measurement target animal raises the stimulation rod. A load (force) applied to the stimulus bar based on the behavior is detected. Details of the animal stimulation / stimulus response detection apparatus 10 will be described later.

  The stimulation control device 20 drives the stimulation rod with respect to the animal to be measured by the animal stimulation / stimulation response detection device 10 according to a command from the measurement / command device 30, its rising time (stimulation time), the interval of stimulation, and the number of times Etc. are directly controlled. The stimulus control device 20 amplifies an analog signal (detection signal) related to the load data sent from the animal stimulus / stimulus response detection device 10 with an amplifier, and transmits the amplified analog signal to the measurement / command device 30. It is.

  The measurement / command device 30 converts the analog signal sent from the stimulus control device 20 into a digital signal by a built-in A / D converter, and based on the digital signal, the response amount to the mechanical stimulus of the animal to be measured (Reaction amount) is calculated by computer analysis, and the response amount to the mechanical stimulus of the animal to be measured is measured. Then, the measurement / command device 30 stores the information on the response amount obtained as a result of the measurement in an internal memory built in the device and displays it on the display device 40 as necessary. In addition, the measurement / command device 30 issues a command to the stimulus control device 20 and the like, and comprehensively controls the operation in the stimulus response measurement system 100. For example, the measurement / command device 30 is configured by a computer.

  The display device 40 displays measurement results and various information based on the control by the measurement / command device 30.

  The operation input device 50 is a device that inputs various input instructions from a measurer (user) to the measurement / command device 30 as input signals. In FIG. 1, an example of a keyboard is shown as the operation input device 50, but the present embodiment is not limited to this, and may be configured to include a mouse or the like.

  FIG. 2 is a schematic diagram illustrating an example of a schematic configuration of the stimulus response measurement system 100 according to the embodiment of the present invention. Here, the same code | symbol is attached | subjected about the structure similar to the structure shown in FIG. FIG. 2 shows an example of a detailed configuration inside the animal stimulus / stimulus response detection apparatus 10 shown in FIG.

  As shown in FIG. 2, the animal stimulus / stimulus response detection apparatus 10 includes an animal cage 10a and a stimulus generation / detection mechanism unit 10b.

  The animal cage 10a is provided with an animal chamber 11 that houses the animal 200 to be measured, and a movable shutter 12 that demarcates a region in the animal chamber 11 that houses the animal 200 to be measured. Here, FIG. 2 shows a mouse as an example of the animal 200 to be measured. In addition, a stimulation rod 13 is provided across the animal cage 10a and the stimulus generation / detection mechanism unit 10b to give a mechanical stimulus such as a light contact stimulus to the animal 200 to be measured housed in the animal chamber 11. It has been.

  In the stimulus generation / detection mechanism unit 10b, when the stimulus target 13 and the target animal 200 to be measured are mechanically stimulated by the stimulus bar 13, the behavior of the target animal 200 to the stimulus stick 13 is changed. There is provided a load sensor 14 which is a detecting means for detecting a load (force) applied to the stimulation bar 13 based thereon. In the example shown in FIG. 2, the load sensor 14 is fixed to the base of the stimulation bar 13. Further, the stimulus generation / detection mechanism unit 10b includes a support 15 for supporting the stimulus bar 13, the load sensor 14, and the like, and a slide rail for moving the stimulus bar drive device 17, the waste tray 18 and the like in the horizontal direction on the left and right. 16 and a slide bar 16 are used to horizontally move the support 15 to horizontally move the stimulation bar 13 left and right, and to move the support 15 vertically to move the stimulation bar 13 vertically. And the filth tray 18 used as the saucer of the filth of the animal 200 to be measured is provided.

FIG. 3 is a photograph showing an example of the appearance of the animal stimulus / stimulus response detection apparatus 10 shown in FIG. FIG. 4 is a photograph showing an example of the appearance of the animal chamber 11 in the animal stimulus / stimulus response detecting apparatus 10 shown in FIG. FIG. 5 is a photograph showing an example of the appearance of the stimulation bar 13 and the load sensor 14 in the animal stimulus / stimulus response detection apparatus 10 shown in FIG.
As shown in FIG. 5, the load sensor 14 is covered with a low columnar metal cover in order to protect the internal precision part from urination and defecation by the animal 200 to be measured.

  In the animal stimulus / stimulus response detection apparatus 10, the animal chamber 11 and the stimulus are stimulated so that the load sensor 14 does not detect a load (force) caused by vibrations caused by self-issued movements such as dressing or posture change of the measurement target animal 200. The rod 13 has a structure that does not come into direct contact with the stimulating rod 13 when it is raised and lowered. In this embodiment, when the stimulation rod 13 rises in the animal chamber 11 and directly touches the measurement target animal 200, the measurement target animal 200 causes a response action to the stimulation rod 13, that is, The load sensor 14 detects the load (force) when the animal 200 to be measured removes the stimulation rod 13 from the hind limb, bites it, or attacks the front limb. From this point of view, in the present embodiment, the following animal stimulus / stimulus response detection apparatus 10 is configured.

(Animal cage 10a)
6 and 7 are photographs showing an example of the appearance of the animal cage 10a in the animal stimulus / stimulus response detecting apparatus 10 shown in FIG. Specifically, FIG. 6 is a photograph of the animal cage 10a taken from above, and FIG. 7 is a photograph of the animal cage 10a taken from above.

  As shown in FIGS. 2, 6, and 7, the animal cage 10 a includes an animal chamber 11 serving as a storage unit for storing the measurement target animal 200, and the measurement target animal 200 within the animal chamber 11. And a movable shutter 12 that demarcates an area for housing the camera. The animal chamber 11 includes a bottom plate for fixing the animal chamber 11 to the housing of the animal stimulus / stimulus response detection device 10. At this time, the animal chamber 11 is formed with an inclined lower portion on the side surface so that the animal 200 to be measured is always located at the center. The bottom plate of the animal chamber 11 is formed with two vertical holes (for example, about 90 mm in length for mice and about 250 mm in length for rats) for allowing the stimulation rod 13 to pass therethrough. ing. Further, the animal chamber 11 is formed with three horizontal holes for inserting the movable shutter 12 at both ends thereof, and the size of the accommodating portion is adjusted according to the size of the animal 200 to be measured. It can be adjusted. Here, in the present embodiment, the animal chamber 11 is of a size that allows the animal 200 to be measured to change its direction in the animal chamber 11 barely. The animal chamber 11 and the movable shutter 12 are made of, for example, colorless and transparent acrylic so that the state of the animal 200 to be measured can be seen from the outside.

(Stimulation bar drive device 17 and stimulation bar 13)
The stimulation rod driving device 17 is a device that drives the stimulation rod 13 by linear motion. The stimulation rod 13 that is brought into contact with the measurement target animal 200 or that is close to the vicinity of the head of the measurement target animal 200 to visually stimulate the measurement target animal 200 is, for example, the long axis of the animal chamber 11. 2 perpendicular to the direction (longitudinal direction), each passing through the two vertical holes of the animal chamber 11 one by one, upwards, at intervals of about 15 mm for mice and about for rats It is attached at intervals of 40 mm.

  As the stimulation rod 13, for example, a rod formed of a metal rod having a diameter of about 3 mm and a length of about 50 mm and having a tip cut into a spherical shape so as not to give pain to the measurement target animal 200 is used. . The driving speed (rising speed) of the stimulating bar 13 by the stimulating bar driving device 17 is variable, and this control is performed based on, for example, an input signal input by the measurer via the operation input device 50. 30 is controlled via the stimulus controller 20. In the stimulation rod driving device 17, for example, the stimulation rod 13 is set to automatically rise into the animal chamber 11 from a vertical hole in the bottom plate of the animal chamber 11 by a linear motion.

  Then, the stimulation rod drive device 17 raises the stimulation rod 13 from the abdominal side of the animal to be measured 200 at a relatively slow speed, for example, a speed of about 85 mm to 100 mm / second, Driving is performed so as to come into contact with the side surface (any one of the hind limb, abdomen, forelimb, neck, and lower jaw) or to stop without contacting the vicinity of the head of the animal 200 to be measured. In addition, the stimulation bar driving device 17 is set to be driven so that the stimulation bar 13 stops at a position of about 10 mm from the bottom surface (bottom plate) of the animal chamber 11 so as not to apply excessive pressure to the animal 200 to be measured. ing. The rise (stimulation) time, the rise (stimulation) interval, and the number of rises (stimulation) of the stimulation rod 13 by the stimulation rod driving device 17 are based on, for example, an input signal input by the measurer via the operation input device 50. Thus, the measurement / command device 30 is automatically controlled and set via the stimulus control device 20.

  In the above description, the stimulating rod driving device 17 horizontally moves the support 15 on the slide rail 16 and horizontally moves the stimulating rod 13 left and right. Alternatively, the stimulation bar 13 may be driven only in the vertical direction, and the movement of the stimulation bar 13 in the horizontal direction on the left and right may be manually performed. In any case, since the animal 200 to be measured changes its position in the animal chamber 11, it is essential that the stimulation rod 13 can be moved in the horizontal direction according to the position of the animal 200 to be measured. In the experiment described later, the temperature in the laboratory is maintained at 23 ± 2 ° C. so as not to stimulate the thermal sensation of the animal 200 to be measured, and the animal stimulation / stimulus response detection apparatus 10 starts the experiment. The temperature of the stimulation bar 13 was controlled by installing it in the laboratory one hour or more before.

(Load sensor 14)
By raising the stimulation rod 13 from the bottom surface of the animal chamber 11 and bringing it into contact with the abdomen or hind limb of the animal 200 to be measured, the animal 200 to be measured dislikes the contact and disposes the stimulation rod 13 with the hind limb. May cause behavior (contact stimulus response behavior). In addition, when the stimulation rod 13 is raised near the face of the animal 200 to be measured, an action (objective attack behavior) of biting the stimulation rod 13 or applying an attack with the forelimbs may occur.

  Normal animals often do not show a significant response to such stimuli, but animals with depressive symptoms often experience severe “contact stimulus response behavior” or “objective attack behavior”. . In the stimulus response measurement system 100 according to the present embodiment, the measurement target animal 200 detects the load (force) applied to the stimulus bar 13 when the target animal 200 kicks the stimulus bar 13 or bites the stimulus bar 13. Therefore, the load sensor 14 for mounting is directly attached to the base of the stimulation rod 13.

  A detection signal related to a load (force) detected by the load sensor 14 (a detection signal related to a load (force) applied to the load sensor 14) is input to the measurement / command device 30 via the stimulus control device 20 and incorporated therein. Analog / digital conversion is performed by the A / D converter. The measurement / command device 30 quantitatively measures a response (reaction) to the stimulus of the animal 200 to be measured based on the load (force) detected by the load sensor 14. Specifically, in the measurement / command device 30, a product of a physical quantity (here, a load (force) applied to the load sensor 14) related to the magnitude of the load (force) detected by the load sensor 14 and its duration ( By calculating a load × time (mN · ms) by computer analysis, a response (response) to the stimulus of the animal 200 to be measured is quantitatively measured. In the stimulus response measurement system 100 of the present embodiment, the measurement result is displayed on the display device 40 and recorded in an internal memory built in the measurement / command device 30. In this way, the response behavior of the measurement target animal 200 to the contact stimulus or the like is quantitatively evaluated, and further, the depression state of the measurement target animal 200 can be quantitatively evaluated.

  In addition, the load sensor 14 detects the magnitude of the load (force) of the contact stimulus response behavior and the objective attack behavior caused by the measurement target animal 200 with respect to the stimulus bar 13 as a vector in the three-axis directions of the XYZ axes. . Further, the display device 40 combines the detected value in the three-axis direction detected by the load sensor 14 by the processing of the measurement / command device 30, and the X-axis and the Y-axis which are horizontal loads (forces). The detected value of the vector is displayed as a waveform with the load (force) (mN) on the vertical axis and the time (ms) on the horizontal axis. The display device 40 displays the measurement result (integrated value) of the response behavior of the animal 200 to be measured for each stimulus. Since this measurement result excludes the load due to the weight of the animal 200 to be measured and sets the load only in the horizontal direction, the detection value of the downward vector (in the Z-axis direction) is excluded from the measurement. That is, in this case, the measurement / command device 30 analyzes the data of the load (force) detected by the load sensor 14 and calculates the horizontal combined vector of the X axis and the Y axis of the load as a response amount. Then, the response amount to the stimulus of the animal 200 to be measured is measured. In the present embodiment, the load sensor 14 is configured as a triaxial load sensor (load cell) that detects the magnitude of the load (force) as a vector in the triaxial direction, but the magnitude of the load (force) is determined. It may be configured as a biaxial load sensor (load cell) that is detected as a vector in the biaxial direction (horizontal direction) of the X axis and the Y axis.

FIG. 8 is a schematic diagram showing an example of a user interface screen displayed on the display device 40 shown in FIG.
In the user interface screen shown in FIG. 8, an animal ID setting unit 801 for the animal 200 to be measured is provided. Further, the user interface screen shown in FIG. 8 is configured so that various stimulation conditions (interval indicating stimulation interval, stimulation time, number of stimulations, and rising / lowering speed of the stimulation bar 13) can be set by the stimulation condition setting unit 802. ing. Further, the user interface screen shown in FIG. 8 includes a display area 803 for displaying information such as a measurement integrated value for each stimulus, a response of the animal 200 to be measured, and a load graph (horizontal load graph, triaxial load graph). A display area 804 for displaying is provided. Further, the user interface screen shown in FIG. 8 is provided with a response action confirmation button (“Reaction [End] button 805” in FIG. 8) and an invalid data button (“Invalid data [Esc] button 806” in FIG. 8). .

  The response action confirmation button is used as an aid to the experiment recording, particularly when the measurer confirms that the response to the stimulus of the animal 200 to be measured is remarkable. The invalid data button is used to determine whether to exclude the measurement value from the recording when the measurement subject presses the animal 200 to be measured during a stimulus, such as body posture change or grooming, when the exercise is unrelated to the stimulus. Used for reference. Here, the number of stimulations is set to a maximum of 5 times depending on the number of times the invalid data button is pressed.

Furthermore, a “measurement start” button 807 and a “measurement end” button 808 are provided on the user interface screen shown in FIG. When the “measurement start” button 807 is pressed by the measurer, the measurement process is started, and when the “measurement end” button 808 is pressed by the measurer, the measurement end process (application end process) is performed. The stimulus response measurement system 100 is calibrated every time immediately before the measurement is started, and the information is displayed on the lower left of the user interface screen shown in FIG.
Also, in the load graph display area 804, a screen ("horizontal load" screen) that displays the horizontal load only in the horizontal direction (the combined vector of the X and Y axes) and all three axes of the XYZ axes are displayed. A screen (“3-axis load” screen) is displayed. In addition, the user interface screen shown in FIG. 8 is provided with a display area 809 indicating the current number of trials.

  Next, an actual experiment using a mouse as the animal 200 to be measured will be described.

(Mouse used as target animal 200)
In this experiment, a ddY mouse was used as the animal 200 to be measured. First, 5 pairs of normal female and male mice were mated to obtain offspring. After giving birth, breastfeeding was carried out as usual, with parents and pups living together for up to 3 weeks after birth. On the 21st day after birth, the pups were weaned. Fifteen of the male offspring were used for measuring the response amount by the contact stimulus response behavior and the objective attack behavior using the stimulus response measurement system 100 of the present embodiment. This is because males do not have a sexual cycle, so there are no behavioral changes due to cyclic changes in sex hormones.

(Stimulus response behavior experiment before isolation and subsequent breeding)
In the fourth week after birth, 15 weaned male pups were subjected to a stimulus response behavior test regarding contact stimulus response behavior and objective attack behavior before isolation. The male offspring mice for which this pre-isolation experiment was completed were divided into two groups, and nine offsprings in the first group were isolated and housed only in one cage (depression model). Six litters of 6 litters in the same litter group were housed in a single cage (control group mice).

(Production of depression mice)
Since mice have the instinct for group life, they are subjected to strong loneliness stress when placed in an isolated environment. Continued strong stress is one of the greatest risk factors for developing depression, so depression occurs in many of the long-term isolated mice. Biochemical investigations of brain material in isolated mice have also demonstrated depression. Currently, based on these findings, isolated mice are widely used as depression model mice in the field of depression research.

  Based on this fact, in this experiment, mice were isolated to cause depression. In the first group of mice in this experiment, isolation was continued for 5 weeks, and the response amount was measured by contact stimulus response behavior and objective attack behavior described later in 1 week, 3 weeks, and 5 weeks after isolation. We evaluated the onset of depression and the severity of depressive symptoms from the response amount. Then, the validity of screening of depressed animals and evaluation of depressive symptoms by the stimulus response measuring system 100 of the present embodiment was considered.

(Changes in mice during the isolation period)
Most mice (90% or more) that were kept in isolation showed mental instability (depressive symptoms). The symptom was a violent elimination action (contact stimulus response action) in the hind limb in response to a light contact stimulus that touched the body, or an avoidance action that left the place. Also, in a narrow place where movement is not possible, an attacking action was taken against an object presented near the face.

  Next, the experimental results using these depression model mice will be described.

In this experiment, the measurement was performed twice in succession with different stimulation positions for the same animal.
FIG. 9 is a schematic diagram illustrating an example of a position where stimulation is performed by raising the stimulation rod 13 with respect to a mouse that is the animal 200 to be measured.
The first time, the stimulus bar 13 was raised to the hind limb level 1 in FIG. 9 and the contact stimulus response behavior was measured. The second time, immediately after the completion of the first stimulus response experiment, the stimulus bar 13 was raised to the head level 2 in FIG. 9 and the objective attack behavior was measured.

(Measurement of response based on contact stimulus response behavior)
The measurement of the contact stimulus response behavior was performed by pushing up the hind limb of the mouse or the abdomen near the hind limb (hind limb level 1 in FIG. 9) with the two stimulation bars 13 from the bottom.

  When the mouse had depression symptoms, the mouse disliked the stimulation with the stimulating bar 13 and often caused the contact stimulus response behavior. Specifically, a mouse with depressive symptoms can either violently remove (kick) the stimulating bar 13 with the hind limb with respect to the contact with the stimulating bar 13, or lift the hind leg high in order to avoid contact with the stimulating bar 13, Alternatively, the body was shaken to endure the contact with the stimulation bar 13. In this experiment, the response behavior to these stimulus bars 13 is collectively referred to as “contact stimulus response behavior”. When these response behaviors appear, the load (force) is detected by the load sensor 14 installed at the base of the stimulus bar 13, and the measurement / command device 30 measures the response amount to the stimulus by computer analysis, The measurement results are displayed on the user interface screen (see FIG. 8) of the display device 40 as a load graph and numerical values.

  In the case of a normal mouse, in many cases, the mouse did not move indifferently with respect to the contact with the stimulation bar 13. However, even in a normal mouse, when some kind of stress was applied before the experiment, the mouse became mentally irritated and sometimes caused contact stimulus response behavior. Therefore, when accommodating the mouse which is the animal to be measured 200 in the animal chamber 11, it is necessary to take care not to stimulate the mouse excessively.

  In this experiment, the mouse was placed in the animal chamber 11 and left for about 10 minutes to acclimatize the mouse to the environment of the animal chamber 11. Moreover, the stimulation conditions in this experiment were as follows. The ascending speed of the stimulating bar 13 was 85 mm / second, the stimulating time (rising time of the stimulating bar 13) was 1 second, the stimulation interval (interval) was once every 10 seconds, and the number of stimulations was 30 times. And in this experiment, the measured value concerning the response amount of 30 times of the number of stimuli was averaged to obtain the response amount of the contact stimulus per one stimulus. As a result of conducting various preliminary experiments, this stimulation condition was determined to be able to measure the mouse response behavior most appropriately, and this condition was set as a common stimulation condition in all experiments. The measurement condition is input to the measurement / command device 30 by the measurer using the user interface screen and the operation input device 50 shown in FIG. 8, and the measurement / command device 30 receives the animal via the stimulus control device 20. It is set by controlling the stimulus / stimulus response detection apparatus 10. In addition, in the measurement, the measurer may change the posture of the mouse during stimulation, grooming, and the behavior shown in FIG. The invalid data button (“invalid data [Esc] button 806)” on the interface screen was pressed to exclude it from the measured value.

FIG. 10 is a photograph showing an example of how the mouse of the animal 200 to be measured is housed in the animal chamber 11 of the animal stimulus / stimulus response detector 10.
FIG. 10 shows a state in which the mouse of the animal 200 to be measured is housed in the animal chamber 11 disposed above the two stimulation bars 13. Further, the movable shutters 12 installed at both ends of the animal chamber 11 define an area in which the mouse of the animal 200 to be measured is accommodated in the animal chamber 11.

  FIG. 11 shows contact stimulation of nine depression model mice in each isolation period before isolation, 1 week after isolation, 3 weeks after isolation, and 5 weeks after isolation using the stimulus response measurement system 100 according to the embodiment of the present invention. It is a characteristic view which shows the measurement result which measured the response amount (contact stimulus response action amount) by response action. Specifically, FIG. 11 shows a characteristic of an average value ± standard error of a response amount (measured value) per stimulation.

  In FIG. 11, the group of animals that showed a response level of 1.66 ± 0.28 mNs before isolation had a response level of 3.27 ± 0.95 mNs after 1 week of isolation and 10. The response amount was 47 ± 2.08 mNs, and the response behavior of the response amount of 15.10 ± 2.10 mNs appeared after 5 weeks of isolation. In addition, in the mice of the group-fed animals that was the other control group, almost no increase in the response amount of the contact stimulus behavior was observed, so the response amount of the contact stimulus response behavior in the depression model mouse in the isolated group was remarkable. The increase is believed to be due to stress from isolation. That is, it is found that screening of depressed animals is possible by measuring the response amount based on the contact stimulus response behavior using the stimulus response measuring system 100, and further, the process of onset and symptom deterioration can be quantified as a numerical value. It was.

(Measurement of response based on objective attack behavior)
The objective attack behavior of the mouse is behavior such as biting on an object (non-living body) approaching in front of the eyes or attacking an object approaching with the forelimb. In this experiment, the stimulation rod 13 was raised to head level 2 in FIG. 9 to stimulate the mouse. At this time, in many cases, the stimulating bar 13 was raised near the head of the mouse without touching the mouse and stopped in front of the mouse or slightly below or in front of it. Alternatively, the stimulating bar 13 pushes up the lower jaw of the mouse from below and gently lifts the head of the mouse. In the latter case, contact between the stimulation bar 13 and the mouse occurs, but by measuring only the load (force) in the horizontal direction of the stimulation bar 13, the program conditions are set so that the load due to this degree of contact is not recorded. . That is, as long as the mouse does not attack the stimulating rod 13, the measurement value related to the load (force) is set to be almost zero.

  The stimulation conditions in this experiment are the same as in the measurement of the contact stimulus response behavior: the rising speed of the stimulation bar 13 is 85 mm / second, the stimulation time (the rising time of the stimulation bar 13) is 1 second, and the stimulation interval (interval) is 10 Once per second, the number of stimulations was 30. And also in this experiment, the measured value concerning the response amount of 30 times of stimulation was averaged to obtain the response amount of the stimulus per stimulus. This stimulation condition is set by conducting a preliminary experiment, similarly to the above-described contact stimulation response behavior measurement, and is a condition that can measure the objective attack behavior of the mouse most appropriately. Also, in the measurement, the measurer can move the mouse when the stimulating bar 13 lifts the forelimb of the mouse from below, or when the mouse changes its position when the stimulating bar 13 is raised. When an action not related to the objective attack action was observed, an invalid data button (“invalid data [Esc] button 806) on the user interface screen shown in FIG. 8 was pressed and excluded from the measured value.

  In normal mice, when the stimulating bar 13 is raised to head level 2 in FIG. 9, the first few times, interest is shown in the stimulating bar 13, biting lightly, smelling, hating the stimulating bar 13 I sometimes changed the position of my face and the direction of my body. However, it soon became less interested in stimuli and often ignored the stimulating bar 13. This normal mouse biting behavior is considered to be one of the search behaviors, and is clearly different from the aggressive biting behavior (objective attack behavior).

  On the other hand, the depression model mouse often performs an attacking action that bites the stimulation bar 13 that rises from the start to the end of the experiment and attacks the stimulation bar 13 with the forelimbs. In addition, the depression model mouse sometimes bites the stimulation bar 13 and sometimes vigorously shakes the stimulation bar 13 back and forth and right and left. In depression model mice, indifference to the stimulating bar 13 was often not observed during the five-minute experimental period. Such objective attack behavior is considered to be unique to depression model mice, and was found to be useful for screening depressed animals and quantifying depression symptoms.

  FIG. 12 shows an objective attack of nine depression model mice in each isolation period before isolation, 1 week after isolation, 3 weeks after isolation, and 5 weeks after isolation using the stimulus response measurement system 100 according to the embodiment of the present invention. It is a characteristic view which shows the measurement result which measured the response amount (objective attack action amount) by action. Specifically, FIG. 12 shows the characteristics of the average value ± standard error of the response amount (measured value) per stimulation.

  FIG. 12 shows that a group of animals that showed a response of 1.31 ± 0.51 mNs before isolation had a response of 1.84 ± 0.68 mNs after 1 week of isolation, and 4.75 after 3 weeks of isolation. The response amount is ± 1.82 mNs, and the response behavior of the response amount of 8.83 ± 2.10 mNs appears after 5 weeks of isolation. That is, no clear objective attack behavior appears yet around 1 week after isolation, but remarkable objective attack behavior appeared around 3 weeks after isolation, and this symptom increased further in 5 weeks after isolation. Is shown.

  In addition, since the increase in the objective attack behavior was hardly observed in the mice of the group-fed animal group (6 animals) as the other control group, the response amount of the objective attack behavior in the depression model mouse in the isolated breeding group was remarkable. The increase is thought to be due to symptoms developed by long-term lonely stress due to isolation. That is, it has been found that by measuring the response amount based on the objective attack behavior using the stimulus response measurement system 100, it is possible to screen depressed animals and to further quantify the onset and symptom deterioration processes as numerical values.

  From the above measurement results, it was found that both hind limb level 1 stimulation and head level 2 stimulation in FIG. 9 are effective for screening depressed animals and quantifying depression symptoms.

  In the above experiment in which the measurement was continuously performed for about 5 weeks after the isolation of an isolated animal (mouse), the response amount based on the contact stimulus response behavior and the objective attack behavior markedly increased. Is closely related to the onset and severity of That is, it is shown that a significant time-dependent increase in the response amount based on the contact stimulus response behavior and the objective attack behavior can be a behavioral indicator of progression or severity of depression. Therefore, by measuring the response amount based on the contact stimulus response behavior and the objective attack behavior of the animal 200 to be measured using the stimulus response measurement system 100 of the present embodiment, the progression of the depression symptoms of the animal is quantified and evaluated. It can be concluded that it is possible. The stimulus response measurement system 100 of the present embodiment can track the progress (severity) of depressive symptoms in the same animal over a long period of time.

  Next, the above 9 animals were kept in isolation until 8 weeks, and the contact stimulus response behavior amount and the objective attack behavior amount were measured by the same method as described above at 8 weeks. Then, after the measurement, all animals were returned to group breeding in which they lived together in a large breeding cage. Then, in the first week, the second week, and the third week after the start of group breeding, the contact stimulus response behavior amount and the objective attack behavior amount were measured using the stimulus response measurement system 100 of the present embodiment.

  FIG. 13 shows a model mouse in each group breeding period before group breeding, one week after group breeding, two weeks after group breeding, and three weeks after group breeding using the stimulus response measuring system 100 according to the embodiment of the present invention. It is a characteristic view which shows the measurement result which measured the contact stimulus response action amount and the objective attack action amount.

  FIG. 13 shows that an animal group showing a contact stimulus response behavior amount of 18.27 ± 2.77 mNs before the group breeding (isolated breeding 8 weeks) is 9.94 ± 1.72 mNs in the first week after the group breeding is started. This shows that the contact stimulus response behavior amount of 5.86 ± 1.00 mNs was shown in the second week after the start of the group breeding and 5.63 ± 0.89 mNs was shown in the third week after the start of the group feed. That is, it was shown by the result of measurement using the stimulus response measurement system 100 that the contact stimulus response behavior caused by the isolation breeding is reduced by returning to the group breeding.

  Further, FIG. 13 shows that an animal group showing an objective attack behavior amount of 12.94 ± 3.53 mNs before the group breeding (isolated breeding 8 weeks) is 4.95 ± 1. This shows that the objective attack behavior amount was 22 mNs, 3.71 ± 1.16 mNs in the second week after the start of the group breeding, and 3.41 ± 0.89 mNs in the third week after the start of the group breeding. That is, the result of measurement using the stimulus response measurement system 100 indicates that the amount of objective attack behavior caused by isolated breeding is reduced by returning to group breeding.

  The above experimental results quantify and show the contact stimulus response action amount and the objective attack action amount using the stimulus response measurement system 100 according to the present embodiment, so that the healing process of the mouse mania can be observed over time. It shows that it can be proved.

  In animal experiments of antidepressants, it is necessary to track the transition of depression symptoms in animals after administration, but in the method using the stimulus response measurement system 100 of this embodiment, an antidepressant is administered. It is also possible to follow the healing process of depression symptoms in depressed model animals.

  In behavioral experiments, such as the conventional Porsau forced swimming experiment, it is possible to screen depressed animals, but the severity of depression that progresses over time and the reduction of depression after antidepressant administration The process could not be shown numerically using the same animals. On the other hand, in the measurement using the stimulus response measurement system 100 of the present embodiment, the severity and cure of the depression can be easily quantified, and as a result, the progression process and the cure process of the depression are the same animal. Can be followed up. As described above, this has not been possible with conventional experimental methods.

  The measurement of the response amount based on the contact stimulus response behavior and the objective attack behavior measures the response amount of the emotional system to the mechanical stimulus. In other words, the emotion of pleasure / discomfort to the stimulus is detected and digitized. Research equipment having such a function has not been developed so far.

  The emotion described above has no learning effect. That is, behavioral experiments regarding emotional behavior can be repeated over and over using the same animal. This is very advantageous, for example, when assessing the effect of a drug before and after administration of an antidepressant to a depression model animal. There are always learning-effect problems in many other behavioral research methods currently used for antidepressant experiments that are commonly performed. For this reason, experiments using the same animal have poor effectiveness in conventional methods. On the other hand, the depression quantification method based on the measurement of the response amount by the contact stimulus response behavior and the objective attack behavior using the stimulus response measurement system 100 of this embodiment is advantageous in that there is no need to consider the learning effect. This is a highly practical technique. With the recent increase in the number of depressed patients, the need for the development of new antidepressants has increased, and the development of antidepressant drug testing methods using laboratory animals has become necessary. The present invention meets the demand and is considered to have extremely high marketability.

  Whether or not the behavior of the animal is correctly quantified depends on whether or not an almost constant response amount (response amount) is obtained each time for the same stimulus given to the same animal, that is, an animal in the same state under the same conditions It is thought that it can be judged by investigating whether or not the measurement value of the response amount (reaction amount) with high reproducibility can be obtained when the measurement is repeated. In the contact stimulus response experiment and the objective attack behavior experiment used in this experiment, it has been clarified that an almost constant response amount is measured in a continuous two-week test. This indicates that the response amount (response amount) of the contact stimulus response behavior and the objective attack behavior is detected almost accurately by measurement by the stimulus response measurement system 100. The high reproducibility of the experimental data is extremely important for quantifying the response amount (response amount) to the response behavior of the animal, and the measurement using the stimulus response measurement system 100 of this embodiment is a stimulus. It shows that there is reliability in quantifying the response amount (reaction amount) to.

  In addition, the animal stimulation / stimulation response detection apparatus 10 of the present embodiment has a structure that never stimulates thermal pain when stimulating animals. As described above, when an intense thermal pain stimulus is given, an animal causes an escape reflex (flexion reflex or spinal reflex) and tries to escape from the stimulus. When the spinal cord reflex appears, it becomes impossible to accurately detect the reaction of the emotional center. Therefore, the stimulating bar 13 is a thick metal bar having a diameter of about 3 mm, and the tip is rounded. At this time, the reason why the metal is used for the stimulation bar 13 is to prevent the measurement target animal 200 from being damaged by biting the stimulation bar 13.

The brains of depressed model animals are often examined in depressed model animals (rats or mice) produced by isolation breeding, and the following studies have been reported on the mechanism of depression in the brain.
(1) In the prefrontal cortex, nucleus accumbens, and hippocampus, the spontaneous release of serotonin decreases in vitro.
(2) Potassium chloride-induced serotonin (5-HT) release increases in vivo in the prefrontal cortex, nucleus accumbens, and hippocampus.
(3) In the raphe nucleus, the activity of 5-HT _1A receptor induced by stress decreases.
(4) A decrease in tryptophan hydroxylase activity is observed in the midbrain.
(5) 5-HT ₁ receptors decrease in the hippocampus and hypothalamus.
(6) The TH _1A mRNA level in the dorsal hippocampus decreases, and the amount of 5-TH _1A receptor in CA1 decreases.
(7) In the hippocampus, prefrontal cortex, and midbrain, the level of tetrahydrobiopterin (BH ₄ ), which is a common coenzyme for serotonin synthesis and dopamine synthesis, increases.
From these facts, it is clear that isolated rearing causes lesions at least in the serotonin system and dopamine system in the brain, which is considered to be one of the pathological mechanisms of depression.

In humans, depressed suicides generally report abnormalities in the serotonin system in the prefrontal ventral region, α2 receptors in the locus coeruleus, and 5-TH _1A receptors in the raphe nucleus. . In depression patients, reduction of cortical thickness in the frontal orbital area, reduction in cell density, and cell miniaturization have been observed. Therefore, it is considered that a similar pathological pathogenesis exists in humans.

  As described above, the mechanism of depression in the brain is highly common between experimental animals and humans. The stimulus response measurement system 100 according to the present embodiment is not limited to the above-described mouse as the animal 200 to be measured. It is shown that it can be applied to animals.

  Further, in the stimulus response measurement system 100 of the present embodiment, it is determined from the other detailed preliminary experiments that it is appropriate that the stimulus time is 5 minutes from the start of the stimulus and the number of times of stimulation is 30 times. Thereby, highly reproducible data can be obtained in a very short time. Thus, it is a big advantage of the stimulus response measuring system 100 of this embodiment that an experiment can be performed simply.

  In addition, with regard to sensitive contact stimulus response behavior and objective attack behavior of animals that have developed depression due to isolation, animals that have developed depression by other methods, for example, after ingesting dioxins via placenta / milk. Exactly the same behavior has been observed in mice that developed depression. From this, it can be considered that the contact stimulus response behavior and the objective attack behavior are part of depressive symptoms.

  The abandonment action is a very quick movement by the hind limbs, and it is impossible to count the number of times the stimulus bar 13 has been kicked with the naked eye. Therefore, in this embodiment, the load sensor 14 is used to capture the erasure behavior of the animal 200 to be measured, measure it as a response amount (reaction amount) (mNs), and display the measurement result on the display device 40. ing. Therefore, in the present embodiment, it is possible to count the number of kicks by reading a waveform such as a graph displayed on the display device 40, and the kick strength can be measured at the same time. It can be put to practical use as one of these. In addition, objective attack behavior can be used to infer the behavior of the animal's response behavior from the measured graph form, and can also be used as auxiliary data to infer the severity of depression in laboratory animals. is there.

  Finally, an example of the present embodiment will be described with reference to FIG. Here, in the following description, an example in which a mouse is used as the measurement target animal 200 will be described.

  First, a normal mouse (normal mouse group) and a depression model mouse (depression model mouse group) corresponding to the severity of depression are accommodated in the animal chamber 11 and stimulated by the stimulation rod 13. And the response amount (response amount) to the stimulus is stored in the internal memory of the measurement / command device 30 in association with a numerical value indicating the severity of depression.

  Subsequently, the mouse of the animal 200 to be measured is accommodated in the animal chamber 11, and a measurement start instruction (specifically, “Measurement” on the user interface screen shown in FIG. When the “start” button 807 is operated), the measurement / command device 30 drives the stimulation rod driving device 17 via the stimulation control device 20 to stimulate the mouse with the stimulation rod 13 (stimulation step). ).

  Subsequently, the load sensor 14 is the action that the mouse has caused to the stimulation bar 13 when the stimulation is applied to the mouse by the stimulation bar 13 based on the control by the measurement / command apparatus 30 via the stimulation control device 20. The load applied to the stimulation bar based on the above is detected (detection step). Thereafter, the detection signal detected by the load sensor 14 is analog / digital converted by the A / D converter built in the measurement / command device 30 via the stimulus control device 20.

  Subsequently, the measurement / command device 30 measures the response amount (reaction amount) to the stimulation by the stimulation rod 13 of the mouse based on the load (force) detected by the load sensor 14 (measurement step).

  Subsequently, the measurement / command device 30 refers to the response amount (reaction amount) of each mouse that is calculated in advance and stored in the internal memory based on the measured response amount (reaction amount) of the mouse. Then, a numerical value indicating the severity of depression in the mouse 200 to be measured is calculated (calculation step).

  Subsequently, the measurement / command device 30 displays information on the measured response amount (reaction amount) of the mouse and numerical information indicating the calculated severity of depression of the mouse on the display device 40 (display step). ). Here, the user interface screen shown in FIG. 8 does not show numerical information indicating the severity of depression in the measurement target animal 200, but in the stimulus response measurement system 100 of the present embodiment. Numerical information indicating the severity of depression of the mouse can be displayed on the display device 40 by the operation of the operation input device 50 by the measurer.

  According to the stimulus response measurement system 100 of the present embodiment, a load (force) based on an action that the measurement target animal 200 gives a stimulus to the measurement target animal 200 with the stimulation bar 13 and the measurement target animal 200 causes the stimulation bar 13. Is detected by the load sensor 14, and based on the detected load (force), the response amount to the stimulation by the stimulation rod 13 of the measurement target animal 200 is measured by the measurement / command device 30. The depressed state of the animal 200 can be quantitatively evaluated.

  Then, by quantifying the response amount to the stimulus by the stimulus bar 13, the severity of the depression symptoms of the animal 200 to be measured can be calculated.

  In addition, in the stimulus response measurement system 100 of the present embodiment, only the stimulus by the stimulus bar 13 is given to the measurement target animal 200, so that measurement can be performed extremely simply and accurately. Measurement can be repeated without giving a strong stress to the measurement target animal. This is extremely useful when, for example, the effect of an antidepressant is measured over time using the same animal. Moreover, it can be used not only for depressed animals but also for quantitatively measuring animals having hypersensitive sensations, for example.

  Each step of the stimulus response measuring method by the stimulus response measuring system 100 according to this embodiment described above can be realized by the computer CPU executing a program stored in a RAM, a ROM, or the like. This program and a computer-readable storage medium storing the program are included in the present invention.

  Specifically, the program is recorded in a storage medium such as a CD-ROM, or provided to a computer via various transmission media. As a storage medium for recording the program, a flexible disk, a hard disk, a magnetic tape, a magneto-optical disk, a nonvolatile memory card, and the like can be used in addition to the CD-ROM. On the other hand, as the transmission medium of the program, a communication medium in a computer network (LAN, WAN such as the Internet, wireless communication network, etc.) system for propagating and supplying program information as a carrier wave can be used. In addition, examples of the communication medium at this time include a wired line such as an optical fiber, a wireless line, and the like.

Moreover, not only the function of the stimulus response measurement system 100 according to the present embodiment is realized by executing the program supplied by the computer, but also the OS (operating system) or other operating system in which the program is running on the computer. When the functions of the stimulus response measurement system 100 according to the present embodiment are realized in cooperation with application software, or all or part of the processing of the supplied program is performed by a function expansion board or function expansion unit of the computer. Even when the function of the stimulus response measurement system 100 according to the present embodiment is realized, such a program is included in the present invention.

  In addition, the above-described embodiments are merely examples of specific examples for carrying out the present invention, and the technical scope of the present invention should not be construed in a limited manner. . That is, the present invention can be implemented in various forms without departing from the technical idea or the main features thereof.

  Currently, behavioral methods using elevated plus mazes and light and dark boxes are often used as methods for examining mental anxiety of laboratory animals. These behavioral methods focus on observing and analyzing the behavior of animals spontaneously and are reliable for examining animal anxiety. However, these behavioral methods cannot assess animal depression.

  In contrast, in the stimulus response measurement system 100 according to the present embodiment, a slight contact stimulus or the like is given to the animal, and the response to the stimulus is analyzed and quantified to quantify the depression symptoms of the animal. It is. Since the method of this embodiment can measure the degree of mental irritation and mental instability of an animal, the mental state of the animal can be evaluated in a more diversified manner by combining the method so far and the method of this embodiment. It becomes possible to do.

It is a photograph which shows an example of the external appearance of the stimulus response measuring system which concerns on embodiment of this invention. It is a mimetic diagram showing an example of a schematic structure of a stimulus response measuring system concerning an embodiment of the present invention. It is a photograph which shows an example of the external appearance of the animal irritation | stimulation / irritation | stimulation response detection apparatus shown in FIG. It is a photograph which shows an example of the external appearance of the chamber for animals in the animal stimulation and stimulus response detection apparatus shown in FIG. It is a photograph which shows an example of the external appearance of the stimulation stick | rod and load sensor in the animal stimulation and stimulation response detection apparatus shown in FIG. It is a photograph which shows an example of the external appearance of the cage for animals in the animal stimulation and stimulus response detection apparatus shown in FIG. It is a photograph which shows an example of the external appearance of the cage for animals in the animal stimulation and stimulus response detection apparatus shown in FIG. It is a schematic diagram which shows an example of the user interface screen displayed on the display apparatus shown in FIG. It is a schematic diagram which shows an example of the position which raises a stimulation stick | rod with respect to the mouse | mouth which is a measurement object animal, and performs a stimulus. It is a photograph which shows an example of a mode that the mouse | mouth of the to-be-measured animal was accommodated in the animal chamber of the animal stimulus / stimulus response detection apparatus. Using the stimulus response measurement system according to the embodiment of the present invention, the amount of response by contact stimulus response behavior of nine depression model mice in each separation period before isolation, 1 week after isolation, 3 weeks after isolation, and 5 weeks after isolation It is a characteristic view which shows the measurement result which measured this. Using the stimulus response measurement system according to the embodiment of the present invention, the response amount by objective attack behavior of nine depression model mice in each separation period before isolation, 1 week after isolation, 3 weeks after isolation, and 5 weeks after isolation is calculated. It is a characteristic view which shows the measured result. Using the stimulus response measuring system according to the embodiment of the present invention, the contact stimulus response behavior amount of the model mouse in each group breeding period before group breeding, one week after group breeding, two weeks after group breeding, and three weeks after group breeding It is a characteristic view which shows the measurement result which measured objective attack action amount.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Animal stimulation / stimulus response detection device 10a Animal cage 10b Stimulation generation / detection mechanism 11 Animal chamber 12 Movable shutter 13 Stimulation rod 14 Load sensor 15 Support 16 Slide rail 17 Stimulation rod drive device 18 Soil tray 20 Stimulation control Device 30 Measurement / command device 30
40 Display device 50 Operation input device 100 Stimulus response measurement system 200 Animal to be measured

Claims (7)

A stimulation rod that gives stimulation to the animal to be measured;
Detecting means for detecting a load applied to the stimulation bar based on an action of the measurement object animal with respect to the stimulation rod when the stimulation object is stimulated by the stimulation rod;
A stimulus response measurement system comprising: a measurement unit that measures a response amount of the measurement target animal to the stimulus based on a load detected by the detection unit.   The detection means detects a load applied to the stimulation bar when the animal to be measured performs an action on the stimulation bar including an action of removing the stimulation bar and an action of biting the stimulation bar. The stimulus response measuring system according to claim 1, wherein The detection means is composed of a biaxial or triaxial load sensor for detecting the load,
The stimulation response measuring system according to claim 1, wherein the load sensor is attached to a base of the stimulation bar. An animal cage for housing the animal to be measured;
Stimulation rod driving means for driving the stimulation rod with respect to the animal to be measured in the animal cage;
The stimulus response measurement system according to claim 1, further comprising display means for displaying the response amount measured by the measurement means.   The measurement unit analyzes the data of the load detected by the detection unit, calculates a horizontal combined vector of the X axis and the Y axis of the load as the response amount, and measures the response amount. The stimulus response measurement system according to any one of claims 1 to 4, wherein: A stimulation step of applying stimulation to the measurement target animal using a stimulation rod;
A detection step of detecting a load applied to the stimulation bar based on a behavior of the measurement object animal with respect to the stimulation rod when the stimulation object is stimulated by the stimulation rod;
A stimulus response measurement method comprising: a measurement step of measuring a response amount of the animal under measurement to the stimulus based on the load detected in the detection step.   In the measurement step, the load data detected in the detection step is analyzed, a horizontal combined vector of the X axis and the Y axis of the load is calculated as the response amount, and the response amount is measured. The stimulus response measuring method according to claim 6.