WO2020216069A1 - Method of preparing model for non-human primates displaying compulsive ritualistic behavior - Google Patents

Abstract

A method of preparing a model for non-human primates displaying ritualistic behavior. The application aims to remedy the technical defect of a lack of a typical model for animals displaying ritualistic behavior in the art, and discloses a method of inducing animals to display ritualistic behavior. The method can be used to obtain a typical ritualistic behavior model for animals in less time, and performs well in the field of ethology.

Description

Method for preparing non-human primate animal model with forced ritual-like behavior Technical field

The present invention belongs to the field of zoology. More specifically, the present invention relates to methods for inducing ritual-like behaviors in non-human primates.

Background technique

Due to the obvious species differences between rodents and primates, especially when it comes to higher brain functions such as emotions, whether the experimental conclusions obtained in the mouse model are equally applicable to primates remains to be further clarified.

The nervous system of non-human primates (such as rhesus monkeys) is closer to humans in terms of structure and function. However, it is currently difficult to establish primates in view of life habits and other reasons such as the lack of language expression ability of animals. An animal model of animal ritual-like behavior.

So far, there is no recognized non-human primate ritual-like behavior model at home and abroad.

Summary of the invention

The purpose of the present invention is to provide a method for preparing non-human primate animal models with ritual-like behavior.

In the first aspect of the present invention, a method for preparing a non-human primate animal model with ritual-like behavior is provided, the method includes: (1) raising the non-human primate animal in a breeding cage alone, so The volume of the breeding cage is limited; (2) Observe animal behaviors during a fixed period of time, and select non-human primates that have ritual-like behaviors; among them, the ritual-like behaviors are more than 70% Next, a combination of several (such as 2, 3, 4, or 5) stereotyped behaviors occurs repeatedly in time sequence; wherein, the stereotyped behavior is an animal frequently repeating a specific posture or behavior.

In a preferred example, the cumulative occurrence time of the specific posture or behavior in a single day is at least 1 hour (such as 1 to 6 hours, and further such as 2, 3, 4, and 5 hours); preferably, the specific posture or behavior Including: clockwise rotation (such as a circle along the cage), counterclockwise rotation, head shake, somersault, and rotation.

In another preferred example, the ritual-like behavior is a combination of several (such as 2, 3, 4, or 5) stereotyped behaviors that occur in an animal that is more than 80% of the time; preferably, The cumulative occurrence time in a single day is at least 1 hour (such as 1 to 6 hours, and further such as 2, 3, 4, and 5 hours).

In another preferred example, the volume of the breeding cage is 20 to 200 times the volume of the non-human primate; preferably 30 to 80 times.

In another preferred example, when the non-human primate is a young rhesus monkey (preferably 2-8 years old, more preferably 3-7 years old), the length of the breeding cage is 600 ~1000mm; width is 600~1000mm; height is 600~1000mm.

In another preferred embodiment, when the non-human primate is a young rhesus monkey (preferably 2-8 years old, more preferably 3-7 years old), the length of the breeding cage is 700 ～900mm; width is 700～900mm; height is 700～900mm.

In another preferred example, the fixed time period includes at least 4 time periods selected from the following group, preferably at least 5 time periods, and more preferably at least 6 time periods:

(a) Observe for 5 to 15 minutes in the time period selected from 7:30 to 8:30;

(b) Selected from 8:30～9:30, observe for 5～15 minutes;

(c) Selected from 9:30～10:30, observation for 5～15 minutes;

(d) Selected from 10:30-11:30 time period, observation for 5-15 minutes;

(e) Selected from 12:30 to 13:30, observation for 5 to 15 minutes;

(f) Selected from 13:30～14:30, observation for 5～15 minutes;

(g) Selected from 14:30-15:30 time period, observation for 5-15 minutes;

In addition, the time periods (a) to (g) are at least 30 minutes apart, preferably at least 40 minutes, and more preferably 45-50 minutes apart.

In another preferred example, the ritual-like behavior is a forced ritual-like behavior.

In another preferred example, the compulsive ritual-like behavior is further combined with other judgment features, such as some drug tests, imaging tests, and emotional observation, so as to be determined as a compulsive ritual-like behavior.

In another preferred example, monitoring is set up by installing surveillance video equipment in the room where the breeding cage is placed.

In another preferred embodiment, the non-human primates include animals selected from the following group: monkeys, gibbons, orangutans; preferably, the monkeys include monkeys selected from the following group: rhesus monkeys, Crab-eating monkey, Japanese macaque, green monkey, marmoset, squirrel monkey.

In another preferred embodiment, the method is a non-diagnostic and non-therapeutic method.

In another aspect of the present invention, the application of the non-human primate animal model obtained by the aforementioned method is provided to study the ritual-like behavior of animals or humans.

In a preferred embodiment, the use is a non-diagnostic and non-therapeutic use.

In another aspect of the present invention, there is provided a method of observing a non-human primate animal model, the method comprising: raising the non-human primates individually in a breeding cage, the volume of the breeding cage is Limited; video recording of animals, preferably for more than 5 weeks (such as 6-12 weeks), observe the following characteristics of animals: (i) Repeat a specific posture or behavior frequently without obvious purpose, preferably The accumulative duration of occurrence of the specific posture or behavior in a single day is at least 1 hour; preferably, the specific posture or behavior includes: clockwise rotation (such as rotation along the cage), counterclockwise rotation, head shaking, somersault, and rotation.

In a preferred example, it also includes the following characteristics of the observed animal: (ii) When more than 70%, more preferably more than 80%, several species (such as 2, 3, 4, or 5) that occur sequentially are selected from (i) A combination of actions; preferably, a single day accumulatively occurs for at least 1 hour.

In another preferred example, the method further includes: observing the time of the first occurrence of (i) or (ii), the time of the last occurrence of (i) or (ii), and/or the first and last occurrence of Time span; and/or observe animal feeding behavior.

In another preferred example, the volume of the breeding cage is 20 to 200 times the volume of the non-human primate; preferably 30 to 80 times.

In another preferred example, when the non-human primate is a young rhesus monkey (preferably 2-8 years old, more preferably 3-7 years old), the length of the breeding cage is 600 ~1000mm; width is 600~1000mm; height is 600~1000mm.

Other aspects of the present invention are obvious to those skilled in the art due to the disclosure herein.

Description of the drawings

Figure 1. The effect of Fluoxetine on the amount and duration of stereotyped behavior in experimental monkeys. In the figure, "before administration" is listed as the data before fluoxetine administration, that is, the specific number of ritual-like behaviors (A) for a specific time period of the day (a total of 6 10-minute data are counted in a single day) And time (B).

(A) The total amount of stereotyped behavior in the fluoxetine group (3) and the control group (2) of experimental monkeys before drug treatment, the second week, the fourth week, the sixth week and the eighth week over time;

(B) The result that the length of stereotyped behavior changes with the increase of the time of drug treatment.

(C) and (D) are the standardized data of (A) and (B) respectively.

Detailed ways

Aiming at the technical defect that there is no typical ritual-like behavior animal model in the field, the inventors have conducted in-depth research and revealed a method for inducing animals to undergo ritual-like behavior. The method can obtain typical ritual behaviors in less time. The animal model of ritual-like behavior has remarkable behavioral performance.

As used herein, the "ritual (like) behavior" or "ritual (like) action" refers to: when an animal exceeds 70%, and more preferably exceeds 80%, several kinds (such as 2, 3, 4, or 5) a combination of stereotypes; that is, the repetition of several stereotypes occurs strictly in a specific order when more than 70%, and more preferably more than 80%, occur. For example, an experimental animal exhibits three stereotyped actions, named A, B, and C respectively. In most cases, the occurrence of these three actions must follow a specific order, such as A→B→C→A→B→ C...A→B→C).

As used herein, the "stereotyped behavior" refers to: an animal repeats a specific posture or behavior frequently without obvious purpose, preferably the specific posture or behavior occurs for at least 1 hour in a single day; Specific postures or behaviors generally include: clockwise rotation (such as a circle along the cage), counterclockwise rotation, head shaking, somersault, and rotation. In this field, stereotyped behaviors are usually not equated with disease states, but that the occurrence of such behaviors has no obvious purpose.

The inventors have been observing the habits and performance of non-human primates for a long time, and after research and optimization, provided a method for preparing a non-human primate model with ritual-like behavior, including: Non-human primates are individually reared in breeding cages, and the volume of the breeding cage is limited. Observations are made at a fixed time period to select non-human primates that have ritual-like behaviors.

The inventors found that raising non-human primates alone is necessary for inducing animals with ritual-like behaviors, while raising them in groups does not easily induce such tendencies in animals. Therefore, in the present invention, non-human primates are individually raised in breeding cages.

On the basis of individual rearing, the inventors also found that the proper size of the rearing cage is also a key aspect in inducing ritual behaviors of non-human primates. A cage that is too large or too small will reduce the induction efficiency or cause Animals produce other atypical states. If the cage is too large, it generally cannot or can only induce a single stereotyped movement; if it is too small, it generally cannot or can only induce the stereotyped movement of some parts of the animal's body, such as head shaking, which is too large or too small. Cannot induce typical ritual-like behavior. Therefore, the inventors set the volume of the breeding cage to be 20-200 times the volume of non-human primates; preferably 30-80 times. In a preferred embodiment, the present inventor selects the non-human primate as the young rhesus monkey. As a preferred mode of the present invention, for this species of non-human primate, the length of the breeding cage is 600 ~1000mm; width is 600~1000mm; height is 600~1000mm.

The method for measuring animal volume is known in the art and can be converted by animal weight. For example, it is known that the density of non-human primates is basically close to the density of water. Assuming that such animals weigh 50 kg, their volume is: 50/1000 cubic meters, or 0.05 cubic meters.

The present inventors also carefully observed the living habits, eating habits, work and rest habits of non-human primates, etc. On this basis, a fixed time period suitable for observing and screening ritual-like behavior animals was optimized. The fixed time period includes at least 4 time periods selected from the following group, preferably at least 5, more preferably at least 6 time periods: (a) a time period selected from 7:30 to 8:30 Observe for 5-15 minutes; (b) Select from 8:30 to 9:30, observe for 5-15 minutes; (c) Select from 9:30 to 10:30, observe for 5～ 15 minutes; (d) selected from 10:30-11:30 time period, observation for 5-15 minutes; (e) selected from 12:30-13:30 time period, observation for 5-15 minutes; (f) Selected from 13:30-14:30, observation for 5-15 minutes; (g) selected from 14:30-15:30, observation for 5-15 minutes; and, above (a)～(g) The time period of) is at least 30 minutes apart, preferably at least 40 minutes, and more preferably 45-50 minutes apart. The inventors have observed that by observing and selecting animals during this period of time, it is easy to observe typical behaviors. The movements of non-human primates are more frequent, and the probability of regularity is high, and the reproducibility is good. Moreover, non-human primates are also prone to anxiety and anxiety-like emotions during these periods of time, which helps to increase the probability of ritual-like behaviors, thereby facilitating the selection of target animals.

In the specific embodiment of the present invention, the non-human primate rhesus monkey is used as the research object, and normal and healthy experimental monkeys are raised in phases in single cages to induce ritual-like behavior. The "staged single-cage rearing", "staged" means that the feeding time is greater than or equal to 4 weeks; the size of the rearing cage for single-cage rearing meets the following requirements: the length range is 600 mm-1000 mm; the width range is 600 mm-1000 Mm; the height range is 600 mm-1000 mm. It was found that the above conditions are beneficial to induce and observe the ritual-like behavior of the experimental monkeys. Further, the present inventors can obtain the target animal model by screening from monkeys that stably exhibit this behavior.

In the specific embodiment of the present invention, the animal model obtained by the screening method of the present invention has typical ritual-like behaviors. The inventors have observed and found that monkey ritual-like actions have the following characteristics:

a. The monkey ritual-like action on a single day takes more than or equal to 2 hours and lasts for 2 weeks or more;

b. The occurrence of ritual-like actions affects the normal eating behavior of the experimental monkeys;

c. Stress can induce monkey ritual-like actions or accelerate the speed of actions that are occurring.

The present inventors also used selective serotonin reuptake inhibitors such as fluoxetine to study whether the mechanism by which the "ritual-like behavior" defined and discovered in the present invention is induced involves the serotonin transmitter system in the brain. As a result, it was found that after such medicinal drugs were administered, the time of occurrence of single-day ritual-like actions of experimental animals was significantly reduced compared to before administration. This result suggests that the induction of ritual-like behavior may involve the serotonin system in the brain.

The present invention also provides the application of the non-human primate animal model obtained by the method to study the ritual-like behavior of animals or humans; alternatively, it can also be combined with other judgment standards or phenotypic observations to judge animals or Human compulsive ritual-like behavior, compulsive-like behavior or compulsive behavior.

The beneficial effects of the present invention are mainly reflected in:

1. A simple and convenient method for obtaining an animal model of non-human primate ritual-like behavior is provided. The animal model obtained by this method has remarkable behavioral performance. The inventor's repeated experiments show that the method has ideal reproducibility.

2. It fills up the gap in the current basic research field and clinical research field in urgent need of suitable animal models (especially non-human primate models). The model can be used to screen and curative effects of drugs and physical interventions for mental diseases. evaluation of.

3. Given that non-human primates are closely related to humans and have similar brain structures and functions, this animal model has great research significance and is widely used.

4. Technical personnel in the field of animal research have not raised and paid attention to the occurrence of the timing of several stereotyped movements, and no one associates this phenomenon with ritual-like behavior. Therefore, the technical solution of the present invention is unexpected to those skilled in the art.

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods that do not indicate specific conditions in the following examples usually follow the conventional conditions or the conditions recommended by the manufacturer.

Materials and Methods

For young (4-7 years old) rhesus monkeys, refer to the following for cage sizes, and refer to international standards for other breeding standards.

Video equipment: Hikvision surveillance system (purchased in Hikvision franchise stores), mainly including Hikvision DS-7100 series hard disk video recorder and 4 sets of 2 million pixel infrared surveillance cameras, 3T Western Digital Surveillance Hard Drive 3 Piece.

40 boxes of Prozac (7 capsules per box, fluoxetine content of 20mg/tablet), provided by Shanghai Mental Health Center.

Unless otherwise stated, stereotyped behavior is defined as: repeating a certain posture or behavior frequently without obvious purpose, the monkey repeats an action, the action includes: clockwise rotation, counterclockwise rotation, head shaking, somersault, Spin.

Unless otherwise stated, ritual-like actions are defined as: a combination of several stereotyped actions that occur repeatedly in time sequence, that is, a monkey performs a series of stereotyped actions in a certain order, and repeats the series of actions in more than 80% of the cases. For example: an experimental monkey exhibits three stereotyped actions, named A, B, and C respectively. In most cases (more than 80%) of these three actions, they must follow a specific order, such as A→B→C ).

Statistics and analysis

Data collation and summary, the statistical method adopts repeated test analysis of variance;

The data is organized into a table, and the average time span and standard deviation of the first and last stereotyped behaviors each day are calculated.

Part of the data was sorted into tables, and the percentage of eating affected by each experimental monkey was calculated.

Example 1. Observation on the feasibility of group or individual behavior inducing stereotyped behavior

In this example, the monkeys were raised in stages to induce stereotyped behavior. The "phased" means that the feeding time is greater than or equal to 4 weeks. The number of experimental monkeys is 100. Install surveillance video equipment and set up surveillance.

Set up multiple breeding cages, and raise healthy experimental monkeys "single/cage" or "multiple (2~4)/cage". Among them, in the “single/cage” rearing method, the cage is 800×800×800 (length×width×height) mm; in the “2/cage” rearing method, the cage is 1600×800×800 (length× Width×height) mm; for the “3 animals/cage” feeding method, the cage is 2400×800×800 (length×width×height) mm; for the “4 animals/cage” feeding method, the cage is 1600×1600× 800 (length × width × height) mm.

Put monkeys weighing 4 to 7 kg into the cages described in the previous paragraph, and put one or more (2 to 4) monkeys in each cage to observe the monkeys' stereotyped behaviors or ritual-like movements. Daily at 8:00-8:10, 9:00-9:10, 10:00-10:10, 13:00-13:10, 14:00-14:10, 15:00-15:10 Observe in six time periods.

Analysis of the first and last time of daily stereotyped behavior: analysis for 14 consecutive days, the time of the first occurrence of stereotyped behavior and the time of the last occurrence of stereotyped behavior of each experimental monkey in a single day. Each experimental monkey had three meals a day, and whether there were stereotyped behaviors or ritual-like actions within 10 minutes after the feeder fed.

As a result, it was found that monkeys raised only in a "single/cage" state had significantly better results in inducing stereotyped behaviors or ritual-like actions. However, in the breeding state of "more (2~4) animals/cage", it is difficult to observe the occurrence of regular, stereotyped behaviors or ritual-like actions. Therefore, in the subsequent embodiments, the monkey is raised in the "single/cage" state.

Example 2: Selection of breeding cage

In this example, the monkeys were raised in stages to induce stereotyped behavior. The "phased" means that the feeding time is greater than or equal to 4 weeks. The number of experimental monkeys is 100. Install surveillance video equipment and set up surveillance.

The healthy experimental monkeys were raised in a single cage, and a variety of cages were set up with different sizes, as shown in Table 2, to observe the better cages that induced stereotyped behaviors or ritual-like actions. Multiple breeding cages can be placed in the same or different rooms. In this experiment, about 10 cages are placed in each room.

Table 1. Design of rearing cage

Put monkeys weighing 4 to 7 kg into the cage designed in Table 1, and put only one monkey in each cage, and observe the monkey's stereotyped behavior or ritual-like actions.

Observation time: analysis daily 8:00-8:10, 9:00-9:10, 10:00-10:10, 13:00-13:10, 14:00-14:10, 15:00- 15:10 These six time periods total 60 minutes of data, and record the number of occurrences of each stereotype and the total time of all stereotypes.

Analysis of the first and last time of daily stereotyped behavior: analysis for 14 consecutive days, the time of the first occurrence of stereotyped behavior and the time of the last occurrence of stereotyped behavior of each experimental monkey in a single day. Each experimental monkey had three meals a day, and whether there were stereotyped behaviors or ritual-like actions within 10 minutes after the feeder fed.

It was found that when the length of the cage ranges from 600 mm to 1000 mm (that is), the width ranges from 600 mm to 1000 mm, and the height ranges from 600 mm to 1000 mm, the result of inducing stereotyped behavior or ritual-like movements is significantly more ideal. , In a short period of time can make monkeys have typical stereotyped behaviors and ritual-like actions (a single day accumulated more than 1 hour).

Example 3: Selection of observation time

Raise healthy experimental monkeys in a single cage, set up a variety of cages, and observe the behavior of the monkeys to determine the best time to observe the stereotyped behavior. Multiple breeding cages can be placed in the same or different rooms. In this experiment, about 10 cages are placed in each room.

The size of the rearing cage is 800×800×800 mm. Put monkeys weighing 4 to 7 kg into the cage designed in Table 1, and put only one monkey in each cage, and observe the monkey's behavior.

Analysis of the first and last time of daily stereotyped behavior: analysis for 14 consecutive days, the time of the first occurrence of stereotyped behavior and the time of the last occurrence of stereotyped behavior of each experimental monkey in a single day. Each experimental monkey had three meals a day, and whether there was stereotyped behavior or ritual-like actions within 10 minutes after the feeder fed.

Table 2. Daily observation time

Based on the above observation results, every day at 8:00-8:10, 9:00-9:10, 10:00-10:10, 13:00-13:10, 14:00-14:10, 15: Observation in the six time periods of 00-15:10 is the most ideal, and it is easy to obtain monkeys whose cumulative occurrence time in a single day exceeds 1 hour.

Example 4. Specific observational characteristics of monkeys that induce ritual-like behaviors according to the preferred conditions of the foregoing Examples 1 to 3

Meet the following requirements: the length range is 600 mm ~ 1000 mm; the width range is 600 mm ~ 1000 mm; the height range is 600 mm ~ 1000 mm. Select monkeys that exhibit stereotyped behavior under the condition of staged single cage rearing.

Under the above conditions, daily at 8:00-8:10, 9:00-9:10, 10:00-10:10, 13:00-13:10, 14:00-14:10, 15: Observations are made in six time periods from 00-15:10. After that, 5 rhesus monkeys (male to female ratio 4:1) showing stereotyped behavior were selected for follow-up experiments: 24 hours a day uninterrupted video recording for 10 weeks (video quality requirements: high-definition continuous recording of all behaviors of experimental animals, night Use infrared mode).

1. Analysis of phenotypic characteristics

Basic information of experimental monkeys and phenotypic characteristics of stereotyped behavior: 5 experimental monkeys exhibiting stereotyped behaviors were used. See Table 3 for specific information.

table 3

The results of behavior analysis showed that all 5 monkeys exhibited repeated stereotyped behaviors that strictly followed specific rules, and 4 of them exhibited 2 or more stereotypes, and the occurrence of these stereotypes was strictly sequential (the remaining 1 showed a single The act of turning in a circle around the cage), that is, a monkey ritual-like action occurs.

Because the occurrence of several independent stereotyped actions in monkey rituals strictly follows a certain specific order, combined with other judgment features, such as some drug tests, imaging tests, and emotional observations, it can indicate that the occurrence of monkey rituals may have Compulsive.

2. When the monkey ritual-like behavior occurred

Data analysis for 14 consecutive days found that, on average, the first monkey ritual-like movements of the experimental monkeys occurred between 6:30-7:00 in the morning and the last occurred between 15:50-18:30. The time span of a single day exceeded 9 hours (Table 4 ).

Table 4

3. The influence of monkey ritual behavior on eating behavior

Data analysis for 14 consecutive days found that within 10 minutes after feeding three meals a day, the experimental monkeys showed monkey ritual-like behaviors, accounting for 40-93% of the total feeding times (Table 5), indicating the influence of this behavior The eating behavior of experimental monkeys is described.

table 5

Example 5. Drug test on animals with severe ritual-like behavior

1. Animal selection

Experimental monkeys were screened in the foregoing examples. From 4 experimental monkeys exhibiting 2 or more stereotyped behaviors, 3 were randomly selected as the fluoxetine group, and the remaining 2 were used as the control group. The experimental monkeys in the control group were fed normally, and the fluoxetine group was given 2mg/kg fluoxetine (dissolved in 30 ml of water and drank under the supervision of the experimenter) in the first week, and 4mg/kg fluoride was given only in the eighth week in the second week Xetine, the others are the same as those in the normal control group.

2. Analyze the effect of fluoxetine

The behavior of each experimental monkey was analyzed during the second, fourth, sixth, and eighth weeks of administration. The behavior analysis method refers to the foregoing.

3. Intervention effect of fluoxetine on monkey ritual-like movements

The inventors performed fluoxetine intervention on experimental monkeys in the fluoxetine group for 8 weeks. Video analysis of the rituals of the experimental monkeys before, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after administration The amount and time of such actions.

The analysis results found (Figure 1) that the time and amount of ritual-like actions in the three experimental monkeys decreased significantly after the administration for 2 weeks, and decreased to less than 75% of the pre-administration; two of them were treated with fluoxetine Ting time increases, and the occurrence of ritual-like actions gradually decreases.

in conclusion

The above results indicate that the staged single-cage rearing that meets the specific settings can induce the stereotyped behavior of the experimental monkeys. Further research found that these experimental monkeys all exhibited repetitive stereotyped behaviors that strictly follow specific rules, and some of the experimental monkeys showed two kinds of or The ritual-like actions of the monkey that occur sequentially in the above stereotyped actions; these actions consume a lot of time in the experimental monkeys (at least 2 hours a day for more than 2 weeks); the ritual-like actions of the monkey affect the eating behavior of the experimental monkeys; When under stress, the monkey's ritual-like movements were more intense; after 8 weeks of fluoxetine administration, the time of single-day monkey-like movements of the experimental monkeys decreased to 29%, 48%, and 85% of the pre-administration. %, while the stereotyped behavior time of the two experimental monkeys in the control group did not change significantly.

The above results indicate that in the present invention, the inventors have discovered and defined monkey ritual-like behaviors, and by optimizing modeling conditions, finally prepared non-human primate animal models with ritual-like behaviors.

All documents mentioned in the present invention are cited as references in this application, as if each document is individually cited as a reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (14)

A method for preparing a non-human primate animal model with ritual-like behavior, characterized in that the method comprises: (1) Raising non-human primates individually in breeding cages, the volume of which is limited; (2) Observe animal behaviors in a fixed period of time, and select non-human primates with ritual-like behaviors; Wherein, the ritual-like behavior is a combination of several stereotyped behaviors that occur repeatedly and sequentially in animals in more than 70% of the cases; Wherein, the stereotyped behavior is that the animal frequently repeats a specific posture or behavior. The method according to claim 1, wherein the cumulative occurrence time of the specific posture or behavior in a single day is at least 1 hour; preferably, the specific posture or behavior includes: turning clockwise, turning counterclockwise, and shaking Head, somersault, spin. The method according to claim 1, wherein the ritual-like behavior is a combination of several stereotyped behaviors that occur repeatedly in time sequence when the animal exceeds 80%; preferably, the cumulative duration of occurrence in a single day At least 1 hour. The method of claim 1, wherein the volume of the rearing cage is 20 to 200 times the volume of the non-human primate; preferably 30 to 80 times. The method of claim 1 or 4, wherein when the non-human primate is a young rhesus monkey, the length of the breeding cage is 600-1000 mm; the width is 600-1000 mm; The height is 600-1000 mm. The method according to claim 1, wherein the fixed time period includes at least 4 time periods selected from the following group, preferably at least 5 time periods, and more preferably at least 6 time periods: (a) Observe for 5 to 15 minutes in the time period selected from 7:30 to 8:30; (b) Selected from 8:30～9:30, observe for 5～15 minutes; (c) Selected from 9:30～10:30, observation for 5～15 minutes; (d) Selected from 10:30-11:30 time period, observation for 5-15 minutes; (e) Selected from 12:30 to 13:30, observation for 5 to 15 minutes; (f) Selected from 13:30～14:30, observation for 5～15 minutes; (g) Selected from 14:30-15:30 time period, observation for 5-15 minutes; In addition, the time periods (a) to (g) are at least 30 minutes apart, preferably at least 40 minutes, and more preferably 45-50 minutes apart. The method of claim 1, wherein the ritual-like behavior is a forced ritual-like behavior. The method according to claim 1, wherein the monitoring is set up by installing surveillance video equipment in the room where the breeding cage is placed. The method of claim 1, wherein the non-human primates include animals selected from the group consisting of monkeys, gibbons, orangutans; preferably, the monkeys include animals selected from the group consisting of Monkeys: Rhesus monkeys, cynomolgus monkeys, Japanese macaques, green monkeys, marmosets, squirrel monkeys. The application of the non-human primate animal model obtained by the method of any one of claims 1-9 for studying the ritual-like behavior of animals or humans. A method for observing a non-human primate animal model, characterized in that the method comprises: individually raising the non-human primates one by one in a breeding cage, the volume of the breeding cage is limited; Video recording, preferably lasting more than 5 weeks, observe the following characteristics of the animal: (i) Repeat a specific posture or behavior frequently without obvious purpose, preferably the specific posture or behavior has a cumulative duration of at least one day It is 1 hour; preferably, the specific posture or behavior includes: clockwise rotation, counterclockwise rotation, head shaking, somersault, and rotation. The method according to claim 11, further comprising observing the following characteristics of the animal: (ii) In the case of more than 70%, more preferably more than 80%, a number of sequential occurrences selected from (i) A combination of actions; preferably, a single day accumulatively occurs for at least 1 hour. The method according to claim 11 or 12, further comprising: Observe the time of the first occurrence of (i) or (ii), the time of the last occurrence of (i) or (ii), and/or the time span of the first and last occurrence in a single day of the observation animal; and/or Observe the feeding behavior of animals. The method according to claim 11 or 12, wherein the volume of the breeding cage is 20 to 200 times the volume of the non-human primate; preferably 30 to 80 times; preferably, the When the non-human primate is a young rhesus monkey, the length of the breeding cage is 600-1000 mm; the width is 600-1000 mm; and the height is 600-1000 mm.

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