Common drug dependence experimental methods
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First, the body dependence test: evaluation of the body dependence potential of new drugs, according to the different categories of new drugs, the following aspects must be tested separately:
1. Natural withdrawal test: The natural withdrawal test is a chronic experiment. The experimental animals are usually given the test drugs by dose escalation; some also use the constant method. The withdrawal symptoms of the natural withdrawal test are slow and lasting for a long time, and it is difficult to quantify the withdrawal symptoms. However, it has been possible to quantitatively evaluate the body-dependent potential of opioids in a variety of animals such as mice, rats, dogs and monkeys. The principle of the test is to suspend the drug after continuous administration of the test drug for a period of time, observe the withdrawal symptoms of the animal, compare it with the representative drugs of the same kind, and judge the dependence potential of the test drug according to the severity of the withdrawal symptoms.
2. Substitute test: The surrogate test is to study the ability of the test drug to inhibit the drug withdrawal symptoms, and then to evaluate the similarity of the physical dependence and strength of the test drug and the opioid. However, trials that inhibit withdrawal symptoms may have false positives and false negatives. Some symptoms appear only in certain animals, while others appear in several animals. Therefore, it is very important to evaluate the ability of the test drug to inhibit various withdrawal symptoms.
3. Urging the test: The principle of the test is to give the animal a large dose of the test drug in a short period of time, and then inject the receptor antagonist to observe and record whether there is withdrawal symptoms and their extent. This method is only applicable to opioids of competitive receptor antagonists.
4. Induction test: Most sedative hypnotics have no competitive receptor antagonists, so it is impossible to conduct a stimulating test, and an induction test can be used. The test principle is that an important indicator for judging sedative hypnotics is convulsions. In the natural withdrawal test, animals need to be administered for a long time to have spontaneous seizures after the drug is discontinued, and the induction test can be applied to various methods of convulsions such as auditogenic seizures, pentylene. Pentylenetetrazole convulsions, only subthreshold stimulating intensity is used in the test, they do not cause seizures in normal animals, but animals that are physically dependent on sedative hypnotics, rebounding excitatory during drug withdrawal, the original threshold Lower stimulation may induce convulsions.
Second, the mental dependence test: to evaluate the mental dependence potential of new drugs, can use the "self administration" test, which is an operational behavier test to determine the intensification of intravenous drugs to animals The reinforcing effect is a current internationally accepted test method for assessing the psychotropic dependence potential of drugs. In addition, drug discrimination tests and conditional position preference tests are commonly used.
1. Self-administration experimental method: The self-administration test method is an operational behavioral pharmacology experiment. People can apply the principle of behavioral analysis to study the effect on behavior according to the results of self-administration experiments. Rationale: Dependent drugs have the same potentiating effects as food and water, and can act as enhancers to stabilize stable, conditional, reflexive behavior in animals. A stimulus (such as light) or behavior that does not have a strengthening effect in itself is associated with the administration of the drug in a certain way, and the stimulation or behavior also causes the animal to have a drug-enhancing effect.
2. Drug discrimination test: The drug discrimination test is the same as the self-administration test, and it is an operational conditional behavior test. The principle of the method is also the same. It can determine whether a drug has a stimulating function in controlling behavior, that is, whether the animal can distinguish or distinguish between two or more drugs, and then generate different behavioral responses. Since the animal does not need surgical intubation in the drug discrimination test, the maintenance is relatively easy, and the experiment can be performed for a long time, so the application is wide.
3. Conditional position preference experiment: Conditional position preference experiment is a non-operating behavioral pharmacology experimental method established and gradually improved in 1979. The method is simple and widely used in recent years.