KR-102962607-B1 - Manufacturing method of post-traumatic stress disorder induced animal model and animal model produced thereby

KR102962607B1KR 102962607 B1KR102962607 B1KR 102962607B1KR-102962607-B1

Abstract

The present invention relates to a method for manufacturing an animal model in which post-traumatic stress disorder is induced, an animal model manufactured thereby, and a method for screening drugs for the prevention or treatment of post-traumatic stress disorder using the same. According to the present invention, an animal model is provided that effectively mimics the human body and induces a fear response.

Inventors

박래리종
박경호
이정훈

Assignees

나손사이언스(주)

Dates

Publication Date: 20260512
Application Date: 20230711
Priority Date: 20220711

Claims (7)

A method for preparing an animal model of post-traumatic stress disorder (PTSD), a) A step of restraining the subject for at least 2 hours; b) A step of forcing the subject to swim for at least 30 seconds; c) a step of forcibly drowning the subject for at least 30 seconds; and d) a step of applying at least 5 electric shocks to the subject; It is characterized by passing through, The electric shock in step d) above consists of a waiting time of at least 2 minutes, a sound and light signal of 30 seconds, and an electric shock of 0.5 seconds, and The above animal is a manufacturing method in which humans are excluded.
In Article 1, A manufacturing method characterized in that steps a) to d) of the above manufacturing method are repeated at least twice over a period of at least 15 days.
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A method of manufacturing in which, in claim 1, the animal is a rodent.
An animal model with induced post-traumatic stress disorder, prepared by the manufacturing method of any one of claims 1, 2, and 4.
As a screening method for drugs for the prevention or treatment of post-traumatic stress disorder using the animal model of claim 5, a) a step of treating a completed animal model with a candidate drug; and b) A step of conducting behavioral experiments on a group treated with the candidate drug and a group not treated; A screening method characterized by including
In claim 6, the above behavioral experiment is a screening method in which one or more are selected from the group consisting of cued fear conditioning, WAZM (Water associated zero maze), and HCA (Home cage observation).

Description

Manufacturing method of post-traumatic stress disorder induced animal model and animal model produced thereby The present invention relates to a method for preparing an animal model with induced post-traumatic stress disorder, an animal model prepared thereby, and a drug screening method using the same. PTSD is a severe condition that can lead to extreme fear, anxiety, and depression, resulting in social distancing and other behavioral disorders. It has also been revealed that exposure to highly stressful events during childhood increases the likelihood of adults developing PTSD. 8.1 million Europeans and 11.4 million Americans suffer from PTSD, severely degrading their quality of life. Current medications are non-specific, ineffective, and have numerous side effects, including sedation, potential for abuse, and sexual dysfunction. Consequently, many people continue to suffer from PTSD despite current treatment options, indicating an urgent need for new therapies. Post-traumatic stress disorder (PTSD) is a notoriously difficult-to-treat, pervasive, and severely debilitating mental disorder characterized by flashbacks, emotional numbness, and insomnia, and is associated with mental health comorbidities such as depression. PTSD can result from catastrophic and threatening events, such as natural disasters, wartime situations, accidents, domestic violence, or violent crimes; symptoms typically develop within three months, but may also appear years after the initial trauma. Furthermore, PTSD is particularly prevalent among combat veterans; reports indicate that approximately 17% of Iraq War veterans exhibited symptoms of PTSD. Consequently, there is a continuously increasing need for treatments with fewer side effects and superior efficacy compared to conventionally developed drugs, yet there is currently no clear treatment available. A limiting factor in the development of PTSD treatments is the lack of a valid transformation model. Accordingly, the inventors intend to provide a novel PTSD animal model that can be usefully utilized for testing the efficacy of new compounds and screening drugs. Figure 1 is a schematic illustration of the manufacturing method of the present invention. Figure 2 shows the results of the WAZM behavioral experiment. Figure 3 shows the results of the WAZM behavioral experiment. Figure 4 shows the results of the signal fear condition behavior experiment. Figure 5 shows the overall conditions of the HCA behavioral experiment. Figure 6 shows the total distance traveled and total travel time during the HCA behavioral experiment. Figure 7 shows the isolation time and body temperature during the HCA behavioral experiment. Figure 8 shows the results of principal component analysis performed according to each experimental group. Figure 9 shows the results of a behavioral experiment on new object recognition. As described above, the inventors have completed the invention of a method for manufacturing a PTSD animal model capable of effectively inducing a fear response and appropriately mimicking human fear responses. The present invention provides a method for manufacturing an animal model of post-traumatic stress disorder (PTSD), characterized by undergoing the steps of: a) restraining the subject for at least 2 hours; b) forcing the subject to swim for at least 30 seconds; c) forcing the subject to drown for at least 30 seconds; and d) applying at least 5 electric shocks to the subject. In the present invention, post-traumatic stress disorder (PTSD) refers to a mental disorder that may occur after receiving mental trauma through a severe accident, and may have major symptoms such as hypersensitivity, re-experiencing of the shock, or emotional avoidance or numbness, and preferably may be induced during childhood. The subject may be an animal under 4 weeks of age. By using a subject in childhood or adolescence rather than an adult, susceptibility to PTSD can be increased, allowing for the effective induction of a fear response. Steps a) through d) above may be performed in a chronological order, but are not limited to that order. According to one aspect, steps a) to d) of the above manufacturing method may be repeated at least twice over a period of at least 15 days, preferably on the 4th and 10th days, and more preferably, the forced immersion of step c) may be performed every day for the initial 4 days. According to one side, the electric shock in step d) above may be characterized by a waiting time of at least 2 minutes, a sound and light signal of 30 seconds, and an electric shock of 0.5 seconds, and the waiting, signal, and electric shock may be made into a total of 5 sets or more. According to one aspect, the animal may be a mammal, preferably a rodent, and most preferably a rat, but is not limited thereto. According to another embodiment of the present invention, an animal model with induced post-traumatic stress disorder, prepared by the above-described manufacturing method, is provide