Method for establishing animal models of anxiety and depression

Methods for Establishing Animal Models of Anxiety and Depression Stress, anxiety, and depression are closely related phenomena, and most patients with anxiety and depression have experienced severe psychological stress events. Therefore, stress events are seen as the cause of anxiety and depression, or at least on the basis of genetics, leading to the development of mood disorders. An animal model of anxiety and depression is to place an animal in a series of stressful situations (potential or actual threats, acute or chronic), causing emotional disorders, and then applying specific means to conduct behavioral and physiological indicators. Detection to explore the in-depth mechanisms of this mood disorder, as well as to identify and screen anxiolytics or antidepressants. 1.1 Anxiety Animal Model Anxiety is an expected response caused by pre-knowing but inevitable, impending stress events. It is characterized by fear, worry, nervousness and other mental symptoms, accompanied by palpitations and hyperhidrosis. The autonomic dysfunction such as cold hands and feet is a worry. From an evolutionary perspective, the defense response exhibited by animals is the original component of human fear and anxiety responses. Therefore, the fear-like response exhibited by animals is similar to that of humans, which is the behavioral basis of an animal model of anxiety. Human anxiety reactions are mainly characterized by escapism, escape behavior, and alertness. The same behavioral responses can also be observed in animals. For example, when an animal is faced with an unfamiliar environment, the animal exhibits a range of behavioral and physiological responses, including inhibition of investigative behavior, sluggishness, escape, increased heart rate, urination, and increased plasma corticosterone levels. These responses can be seen as activation of the defense response system in the event of an animal facing a dangerous situation. Therefore, by scientific comparison, humans and animals can be considered to have the same state of anxiety. Research on the biological mechanisms of anxiety and depression has developed rapidly and gradually deepened to the molecular and genetic levels. However, due to the characteristics of the research field, the research on animal models of anxiety and depression has developed relatively slowly. Moreover, researchers tend to use more classical animal models during the application process, which limits their development. 1.2 Behavioral detection methods At present, the commonly used anxiety animal models mainly include two categories: one is based on animal unconditional models, and can be divided into inquiry behavior models and social behavior models according to their behavioral characteristics. The inquiry behavior model mainly includes the comparison of the classic elevated cross maze experiment and the open field experiment. The test puts the animal in the central area of ​​the maze, and then observes the time and number of times the animal enters the open arm and the closed arm respectively within a certain period of time. Because the open arm communicates with the outside world, it has certain novelty and certainity for the animal. Threatening, animals also produce anxiety responses while generating curiosity. If the level of anxiety is high, the animal will retreat from the open arm to the closed arm, otherwise it will stay in the open arm for more time and the number of explorations of the open arm will increase. In the middle area, the central area is a potential threat situation for animals, while the outer area is relatively safe. Therefore, if the animal's anxiety level is high, it tends to stay in the outer area. On the contrary, the number of times and time for the central area will increase. . Using similar principles, Crawley et al. established a clear-black box experiment using animals with natural aversion and curiosity in bright places, and long periods of time when animals escaped from bright areas indicate high levels of anxiety. Social behavior models include exposure to natural enemies, social isolation, and maternal deprivation.

Instrument Model: ZS Behavior The original natural enemy exposure model generally exposes the animal to another animal that is strongly threatening its life, such as exposing the rat to a cat or another male rat with a strong attack ability. Then, the natural enemies will attack the animals violently, which will increase their anxiety level. However, such a model often causes physical trauma. Later, the research found that only the natural enemies or the excretions of the natural enemies were exposed to the animals, and the body attack could not cause a strong anxiety reaction. Therefore, it was widely used later. Models such as exposure to natural enemies and gas exposure to natural enemies. Another type of anxiety model is based on conditioned reflex models, which mainly include drinking water conflict models and conditional electric shocks. Drinking water conflict is the combination of animal drinking behavior and uncertain electric shock. If the animal wants to meet the needs of drinking water, it may be traumatized by electric shock, which causes the animal to avoid conflicts between drinking water and avoiding electric shock, and generate anxiety reaction. In the conditional shock model, a certain signal and electric shock are randomly combined, and an electric shock may occur after the signal appears, or there may be no electric shock, thereby causing an expectant anxiety reaction of the animal. Such models are very effective in simulating human anxiety responses and predicting anti-anxiety drugs, but inevitably include components of physical stress such as electric shock, which increases the proportion of physical stress in psychological stress. Its main flaws. In addition, there are many effective anxiety stress models. The empty bottle stress model recently established by Lin Wenjuan et al. has proved to be an effective anxiety stress model. After several fixed-time drinking water learning, empty bottles of animals during drinking time can induce animal attacks, bite bottles and cages, frequent modification and other anxiety reactions, accompanied by adrenaline, norepinephrine and corticosterone. The increase in level better simulates the behavior and physiological response of human anxiety.

Some of the animal models of anxiety are mainly used to establish animal models, while others can be used to build models and to measure the level of anxiety. Different animal models have different proportions of the two effects, including natural enemy exposure, drinking water conflict, Social isolation and maternal deprivation are often used to build an animal model of anxiety, while elevated cross maze and open field experiments can both model and measure anxiety responses. To prove whether the anxiety model stimulates the animal's anxiety response, it should look for ways and indicators to measure anxiety. The animal's anxiety response is typically measured using the animal's behavioral or physiological response to a stress or new event. These aversive situations in animals include open spaces, bright or high altitudes, all of which form the basis for measuring the anxiety response of animals using inquiry tests. The classic method of measuring animal anxiety is the elevated cross maze test and the open field test. These new environments have potential survival threats to animals. Therefore, the animal's exploratory defense response is stimulated, and the animal's anxiety is reflected by the inquiry behavior. It is based on the two-factor theory of the animal's anxiety level and inquiry behavior under unfamiliar situations. The main behavioral observation indicators include: (1) the inhibition of inquiry behavior, the reduction of the number of explorations of the open arms by the animals, the decrease of the time spent on the open arms, the decrease of the number of exploration spaces in the central grid, and the avoidance of animals in bright places; (2) The fear response increased, the animal's urination, the number of bowel movements increased significantly, and frequent modification; (3) the social behavior decreased, the behavior of mutual odor and mutual pursuit decreased significantly, and the animals tended to escape other animals.