Methods and applications of animal models of obsessive-compulsive disorder

Abstract

This invention relates to a method for constructing an animal model of obsessive-compulsive disorder (OCD). The main feature of this method is that it includes administering sodium succinate to the modeling animals during the modeling period, and obtaining the animal model at the end of the modeling period. Using oral administration of sodium succinate to prepare a mouse model of OCD offers good reproducibility, low cost, and ease of implementation.

Description

Technical Field

[0001] This invention belongs to the field of animal model construction technology, specifically relating to a method for constructing and applying an animal model of obsessive-compulsive disorder. Background Technology

[0002] Obsessive-compulsive disorder (OCD) is a chronic, disabling mental disorder characterized by obsessive thoughts or compulsive behaviors. Obsessive thoughts refer to repetitive, persistent, intrusive, and unnecessary ideas, images, or impulses, often accompanied by significant anxiety; while compulsive behaviors refer to repetitive behaviors or mental activities, which individuals often feel are performed according to strict rules in order to cope with obsessive thoughts.

[0003] Like other mental disorders, obsessive-compulsive disorder (OCD) faces the challenge of unclear pathological mechanisms, which hinders the development of targeted treatments. Animal models of the disease are important tools for further expanding our understanding of the pathophysiological mechanisms of OCD.

[0004] Existing animal models of obsessive-compulsive disorder can be classified into categories based on their preparation methods, such as gene editing, drug-induced, stress-induced, and optogenetic manipulation. However, gene editing and optogenetic manipulation models have drawbacks such as long preparation cycles and high economic costs, while drugs or stress are difficult to stably induce obsessive-compulsive behaviors in animals, and obsessive-compulsive behaviors will gradually disappear as the drugs or stress factors are removed.

[0005] In order to promote in-depth research on the pathophysiological mechanisms of obsessive-compulsive disorder (OCD) and to develop targeted drugs for OCD with good therapeutic effects and high clinical translation potential, it is necessary and urgent to construct an animal disease model of OCD that can stably exhibit obsessive-compulsive behaviors. Summary of the Invention

[0006] To address the aforementioned problems in the prior art, this invention provides a method for constructing and applying an animal model of obsessive-compulsive disorder.

[0007] To achieve the above objectives, a first aspect of the present invention provides a method for constructing an animal model of obsessive-compulsive disorder, characterized in that the method comprises: administering sodium succinate to the modeling animal during the modeling period, and obtaining the animal model at the end of the modeling period.

[0008] Preferably, during the modeling period, the drinking water for the modeling animals is changed every other day, and the drinking water contains sodium succinate solution. The concentration of the sodium succinate solution is 0.015 g / mL.

[0009] Preferably, the animal model is a mouse model.

[0010] A second aspect of the invention provides an animal model of obsessive-compulsive disorder obtained by the aforementioned construction method.

[0011] A third aspect of the invention provides the use of the aforementioned animal model in screening drugs for the prevention and / or treatment of obsessive-compulsive disorder.

[0012] A fourth aspect of the invention provides the application of sodium succinate in the construction of animal models of obsessive-compulsive disorder.

[0013] Preferably, the animal model is the C57BL / 6 mouse model.

[0014] The beneficial effects of this invention are: using sodium succinate for oral administration to prepare a mouse model of obsessive-compulsive disorder is reproducible, economical, and easy to implement. Attached Figure Description

[0015] Figure 1 This is a flowchart illustrating the construction of a mouse model of obsessive-compulsive disorder using sodium succinate, as described in this invention.

[0016] Figure 2 a and 2b show the changes in body weight and daily water intake of mice during oral administration of sodium succinate, respectively.

[0017] Figure 3 a to Figure 3 Figure d shows the results of anxiety-like behavior in mice after oral administration of sodium succinate.

[0018] Figure 4 a to Figure 4 Figure c shows the results of compulsive-like behavior in mice after oral administration of sodium succinate. Detailed Implementation

[0019] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below with reference to specific embodiments.

[0020] In this embodiment of the invention, male C57BL / 6 mice were used as experimental animals and housed in SPF-grade animal barriers under constant temperature and humidity conditions. The light-dark cycle was 7:00-19:00 light and 19:00-7:00 the next day darkness. Five mice were housed per cage, and the mice had free access to water and food. After one week of acclimatization, 8-week-old adult male C57 / BL6 mice began to develop the model.

[0021] Example 1: Sodium succinate modeling

[0022] The experimental animals were divided into two groups: a control group and a sodium succinate administration group, with 10 animals in each group.

[0023] The model was established by oral administration of sodium succinate for a total of three weeks. During this period, the drinking water in the mice's cages was changed every other day. The specific procedure is as follows: Figure 1 As shown.

[0024] For the control group, the drinking water in the water bottles in the mouse cages was the same as that used for normal mice.

[0025] For the sodium succinate administration group, the drinking water in the mice cages was: sodium succinate solution added to the normal drinking water of mice. The sodium succinate solution was prepared by dissolving sodium succinate in the normal drinking water of mice, and the concentration of the sodium succinate solution was 0.015 g / mL.

[0026] During the first and second weeks of drug administration, the mice and their water bottles in the cages were weighed every other day.

[0027] like Figure 2 As shown in a and 2b, during the administration period, there were no significant differences in body weight (repeated measures ANOVA, interaction effect p = 0.0143, time effect p < 0.0001, sodium succinate administration effect p = 0.1895) and water intake (repeated measures ANOVA, interaction effect p = 0.8741, time effect p = 0.0068, sodium succinate administration effect p = 0.1284) between the sodium succinate group and the control group. These results indicate that oral administration of sodium succinate does not affect body weight or water intake in mice.

[0028] Example 2: Behavioral Testing

[0029] For the control group and sodium succinate administration group in Example 1, behavioral tests were conducted at the third week after oral administration of sodium succinate.

[0030] All behavioral tests were conducted within the animals' light-dark cycle. Before each test, mice were placed in the testing room to acclimatize to the environment for at least one hour. The testing room was kept at a constant temperature and humidity, and illuminated with dim lighting. During the tests, the experimental apparatus was sprayed and wiped with 75% alcohol after each test to prevent odor from affecting the mice's behavioral performance in subsequent tests.

[0031] In behavioral testing, the open field test and the elevated cross maze test were used to assess anxiety-like behaviors, while the bead-burying test and grooming behavior were used to assess compulsive-like behaviors. The order of behavioral testing was: open field test, elevated cross maze test, bead-burying test, and grooming behavior.

[0032] Open field test: Mice were placed in the central area of ​​an open field box (40 cm long, 40 cm wide, and 40 cm high) for 10 minutes. The observation indicators were total movement distance, time spent in the central area, and number of times mice entered the central area.

[0033] Elevated cross maze test: Mice were placed facing the open arm in the center of an elevated cross maze (open arm 30 cm long, 5 cm wide; closed arm 30 cm long, 5 cm wide; elevated cross maze 30 cm above the ground) for 5 minutes. The observation index was the proportion of time spent in the open arm.

[0034] Bead embedding experiment: Mice were placed in a mouse cage (26 cm long and 16 cm wide) with 5 cm thick bedding. Twelve glass beads were placed on the bedding surface in a 4-row, 3-column arrangement. The test lasted 30 minutes. The observation index was the number of embedded beads.

[0035] Grooming behavior: Mice were placed in cages with sterile water sprayed onto their heads and faces after a period of time. The test lasted 10 minutes, with 5 minutes recording grooming behavior before and 5 minutes after spraying. The observed indicators were the time when grooming began after spraying, the number of grooming episodes before and after spraying, and the duration of grooming before and after spraying.

[0036] like Figure 3 As shown in a and 3b, in the open field experiment, the total distance traveled by mice in the sodium succinate group in the open field ( Figure 3 a, Kolmogorov-Smirnov test, p = 0.1641) and time spent in the central region ( Figure 3 b, Independent samples t-test, p = 0.7369) showed no significant difference compared to the control group. Figure 3 As shown in c, the number of times mice in the sodium succinate group entered the central area of ​​the open field (independent samples t-test, p = 0.1208) tended to be less than that in the control group. Figure 3 As shown in Figure d, in the elevated cross maze test, the proportion of time mice spent in the open arms of the elevated cross maze in the sodium succinate group (independent samples t-test, p = 0.6057) was not significantly different from that in the control group. This result indicates that oral administration of sodium succinate did not affect the motor abilities of mice, but tended to increase anxiety-like behaviors.

[0037] like Figure 4 As shown in figure a, in the bead embedding experiment, the number of embedded beads in the sodium succinate group (Kolmogorov-Smirnov test, p = 0.4005) was not significantly different from that in the control group. Figure 4 As shown in b and 4c, in the assessment of grooming behavior, the number of grooming episodes in the sodium succinate administration group and the control group before water spraying ( Figure 4 b, Bonferroni multiple comparison test, p > 0.9999) and grooming time ( Figure 4c, Bonferroni multiple comparison test (p > 0.9999) showed no significant difference, while the number of grooming events in the sodium succinate-treated group after water spraying was significantly lower. Figure 4 b, Bonferroni multiple comparison test, p = 0.0232; * indicates p < 0.05) significantly more mice than the control group. This result indicates that oral administration of sodium succinate significantly increased compulsive-like behavior in mice.

[0038] In summary, oral administration of sodium succinate can increase anxiety levels in mice and induce significant compulsive behaviors. Therefore, an obsessive-compulsive disorder mouse model can be established through oral administration of sodium succinate.

[0039] In this specification, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and variations can be made without departing from the spirit and scope of the invention. Therefore, the specification and drawings should be considered illustrative rather than restrictive.

Claims

1. A method for constructing an animal model of obsessive-compulsive disorder, characterized in that, The construction method includes: administering sodium succinate to the modeling animals during the modeling period, and obtaining the animal model at the end of the modeling period; During the modeling period, the drinking water for the modeling animals is changed every other day. The drinking water contains sodium succinate solution. The animal model is a mouse model.

2. The method for constructing an animal model of obsessive-compulsive disorder according to claim 1, characterized in that, The animal model described is the C57BL / 6 mouse model.

3. The application of the animal model obtained by the method for constructing the obsessive-compulsive disorder animal model according to claim 1 in screening drugs for the prevention and / or treatment of obsessive-compulsive disorder.

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