[Animal Modeling]-Establishment and evaluation methods of other drug dependent animal models
动物造模,毒品依赖
z-bo
2022-02-02
438
1. Establish and evaluate animal models of ketamine dependence
The method of ketamine (commonly known as K powder) is a non-competitive N-methyl-D-aspartate receptor antagonist and has an anesthetic effect. It is widely used in clinical medicine, especially in pediatric patients and the heart Among sick patients. In addition. Ketamine is also a commonly used anesthetic in veterinary surgery. Long-term abuse of ketamine can lead to addiction and can severely damage various tissues and organs of the human body. Its destruction mechanism is different from other drugs (morphine, heroin, methamphetamine, etc.). Currently, laboratory animal studies of ketamine mainly use mouse and rat models. Some researchers have used mice as experimental animals by intraperitoneal injection of ketamine (at a dose of 30 mg/kg once a day). The time of administration is combined with the abuse situation and the characteristics of the abused population. There are 6 weeks, 16 weeks and 28 weeks. wait. At the same time, we used ketamine and ethanol (10% ethanol 0.5 ml oral solution) to study the performance and mechanism of central nervous system damage and cardiac function damage caused by the two.
There are also reports that 100 mg/kg was administered once a day for 7 consecutive days of intraperitoneal injection of ketamine hydrochloride. The determination of addiction is mainly based on the symptoms shown by the animals after injection. The rats exhibited the following excitatory symptoms: accelerated breathing, increased respiratory secretions, increased activity and a firm tail upward. With the increase in the number of drugs, the symptoms of restlessness increased significantly, with twisting, standing, jumping, cycling, and all four legs facing up. Some scholars also used cynomolgus monkeys for research purposes, and cynomolgus monkeys (intravenous injection, dose 1 mg/kg) for 6 months as experimental purposes. Researchers performed behavioral assessments (including exercise, walking, climbing, jumping, etc.) in monkey models, detecting neuronal apoptosis in frontal brain tissue, detecting genes related to apoptosis in brain tissue, and long-term ketamine and other factors. Use can cause permanent damage to the brain function of primates.
2. Establishment and evaluation method of cocaine dependence animal model
Cocaine (cocaine), also known as cocaine, is the most common drug abuse in Europe and America. There are many studies on cocaine. The study also established subcutaneous or intraperitoneal injection to establish cocaine dependence animal models. The dose is 15-30 mg/kg, once a day, and the longest administration time is 28 days. Some researchers have used genetically modified mice to study the cocaine-dependent mechanism of intraperitoneal injection, and have performed spontaneous activity tests and conditioned place preference (CPP) experimental tests. The animal activity doses are 5 mg/kg, 10 mg/kg and 20 mg/kg, and the experimental doses preferred in conditional places are 5 mg/kg and 20 mg/kg. The dosing interval was every other day, and the CPP experiment was performed on the 10th day. To summarize the main points, use intraperitoneal cocaine injections, and use exercise activity and CPP test results to determine whether you are addicted. Some researchers have used the rat jugular vein catheterization technique to insert and indwell a silicone cannula, train the rat for 14 days after the operation, and push a special lever to allow the rat to achieve self-administration. I tried to learn. Press the lever once to inject 0.75 mg/kg of cocaine hydrochloride. The researchers also established a cocaine behavioral sensitization model in rats, and cocaine behavioral sensitization model for research. The basic strategy is to use male SD rats aged 21 to 23 days for various treatments. The control group was intraperitoneally injected with saline (1 ml/kg). ), the experimental group was injected with cocaine hydrochloride (15 mg/kg) intraperitoneally once a day for 5 consecutive days. Then stop the medication for 1 to 14 days, then take other drugs or cocaine, and finally perform voluntary activity tests, such as level activity and distance testing. In short, the animal models of cocaine addiction are mainly intraperitoneal or self-administered. The experimental animals used are mainly rats and mice, and behavior (spontaneous activity test and conditional position) preference experiment) to assess whether the animal is drug dependent.
3. In vitro experimental study on drug dependence
In vitro experimental research on drug dependence is also called in vitro experimental research. The method of culturing neurons in vitro is mainly used to administer different drugs to the cultured neurons at different times and doses. Next, we will use various intervention measures to intervene to study the influence and mechanism of intervention measures on drug dependence. In vitro experiments are also commonly used research methods for drug addiction. Commonly used neuronal cultures include cortical neuron cultures from hippocampus, hypothalamus, and isolated embryonic or newborn mice. Various cell lines such as rat pheochromocytoma cell PC12 and human neuroblastoma cell SH-SY5Y have also been used for research, and the neurotoxic effects of drugs and the neuroprotective effects of related drugs have been observed.
