Summary  

Methods The conditional position preference experiment system was evaluated by dose escalation** dependent model blank control method and ** dependent animal self-control method.  
Results From the d3 days after administration, the test animals showed the preference of one side of the experimental kit (with the kit), and the residence time was longer than that of the other side box (non-contained kit) (P<0.01). After morphine is stopped, there is still a preference for the kit.  

In the evaluation of the mental dependence of drugs, the conditional position preference experiment has its unique advantages compared with the self-administration and drug discrimination test methods: the device is simple, the experiment period is short, and the animal is not affected by the operation mode. It will not affect the experimental results because it hinders the exercise function after the test. The greatest advantage of the conditional position preference test method is that it can not only measure the reward effect of the drug, but also measure the aversive effect of the drug. However, this method requires a lot of time in the observation of animal behavior, a large workload, and the experimental data will be human error. At the same time, the use of classic opioids** caused animal models to be evaluated and their systems evaluated.  
1 System Description  

The computer-controlled Conditionplace preference system (CPPS) consists of several experimental boxes and a CPPS-specific microcomputer.  
Each of the experimental boxes is 60 cm long, 30 cm wide and 30 cm high. It is divided into two parts, A and B (with a kit and a non-medicine box). There is a detachable baffle in the middle of A and B. The space of the two different squares is formed, the part A is gray, and the part B is black and white zebra stripe. There are 12 small holes on both sides of part A, respectively, which are equipped with infrared light-emitting diodes and phototransistors. The photo-electric tubes are connected to the microcomputer control system by data transmission lines.  

2 system application

2.1 Materials Wistar rats, weighing 200 ~ 250g; morphine hydrochloride powder.  
2.2 Method  

2.2.1 Self-control method  

The experimental period was 20 days. Animals were injected with morphine once a day (subcutaneous injection, 5 mg*kg-1) in the first 10 days, and normal saline was injected in the afternoon. After morphine injection, the animals were placed in a black and white striped box (with a kit), and after injection of physiological saline, the animals were placed in a gray box (without the kit). Each training time is 60min. The daily injection time per animal was fixed with an error of no more than 3 min. The position preference effect of the animals was tested before administration, administration of d 3, d 7 , d 11 and withdrawal of d 3 , d 7 , d11. During the test, the partition in the middle of the experiment box was raised by 12 cm, and the animals were placed in the middle of the partition, and they were freely selected for each box. At this point, the corresponding parameters are input to the computer, and the system automatically detects the residence time of the animals in the two color boxes (with the kit and the non-contained kit) within 15 minutes.  

2.2.2 dose escalation and blank control  

The experimental period was 20 days, and the animals were randomly divided into the ** group and the control group. Animals were injected with morphine once every 12 h for the first 10 days, and the dose was gradually increased from 15 mg*kg-1 to 90 mg*kg-1 (increasing concentration, 5 mg each time). After morphine injection, the animals were placed in a black and white strip box (with a kit), and the saline group was injected with normal saline. The injection volume and time were the same as those in the morphine group. After the injection, the animals were placed in a gray box (not accompanied). Pillbox) training. The position preference effect of the animals was tested at 60 min each training time before dosing, at doses d3, d7, d10 and at doses d3, d7, d10. During the test, the partition in the middle of the experiment box was raised by 12 cm, and the animals were placed in the middle of the partition, and the boxes were freely selected. At this point, the corresponding parameters are input to the computer, and the system automatically detects the residence time of the animals in the two color boxes (with the kit and the non-contained kit) within 15 minutes.

3 results

3.1 Self-control method Starting from the administration of d3, the test animals showed the preference of one side of the experimental kit (with the kit), and the residence time was longer than that of the other side box (non-contained kit) (P< 0.01), after morphine is stopped, there is still a preference for the kit.  

3.2 Dose escalation and blank control method As with the self-control, starting from the dose of d3, the animals in the ** group showed the preference of one side of the experimental box related to the medication, and the residence time was longer than that on the other side (P<0.05 or 0.01). After the morphine was stopped, there was still a preference for the kit, while the time of the blank control group staying in the kit with the non-contained kit was not significant.  
4 Discussion  

The mental dependence of drugs is an important indicator for evaluating the potential of drug abuse. Following self-administration experiments and drug-discrimination experiments, conditional position preference experiments have gradually become the most convenient and most commonly used experiment for mental dependence of drug-dependent animals. method. The basic principle of the CPP experiment is to match the environmental stimuli with a certain drug as a conditional enhancement, so that the animal establishes a connection between environmental stimuli and drugs, and forms an operational behavior, thereby observing the animal's preference for the collocation environment. With the strengthening effect of drugs. CPP can evaluate a variety of drug-dependent drugs. For some drugs with sedative or muscle relaxant effects, such as diazepam, CPP is more effective than self-administration experiments.