Effect of Fuzheng Oral Liquid on Conditional Location Preference in Drug-Dependent Mice

Effect of Fuzheng Oral Liquid on Conditional Location Preference in Drug-Dependent Mice

Abstract 目的AIM: To observe the effect of Fuzheng Oral Liquid (FZY) on the conditional position preference effect of drug dependent mice. METHODS: A dose-incremental subcutaneous injection of drugs combined with a conditional position preference box was used to establish a conditional position preference (CPP) mouse model. After the mouse UP gradually subsided, the mice were randomly divided into the normal saline group, the drug group (50 m part kg) and the Fuzheng oral liquid low-quantity, medium-dose and high-dose groups (the doses were 1, 2, 4 respectively). m Uk g ) , 5 days after the corresponding drug treatment, subcutaneous injection of hydrocortisone (5 m weight kg) ignited the UP effect, and observed the behavior of each group of mice. RESULTS: The training time of the white box of the trained mice was significantly prolonged, and the drug-induced CPP formation in mice was observed. After the drug was stopped for 12 days, the drug-induced UP of the mice gradually subsided; hydrocortisone and drugs could induce small reproduction. Rat CPP effect, Fuzheng oral liquid each dose group inhibited the recurrence of CPP effect in mice. Conclusion: Fuzheng oral liquid can effectively inhibit the CPP effect of drug dependent mice.

Key words: Fuzheng oral liquid / pharmacodynamics conditional preference for drug nitriding cortisone

CLC number, R 2 8 5 . 5 Document code: B

Opioid addiction manifests itself in both physical dependence and mental dependence: the former is mainly characterized by the withdrawal symptoms after withdrawal; the latter is manifested by the desire of the drug users to repeatedly or repeatedly use drugs in order to pursue a happy feeling. Mental dependence is a psychoactive effect of opioids on the central nervous system and is the main cause of repeated drug use (or relapse) by drug abusers. Drug craving and relapse behavior are closely related to the activation of memory and glucocorticoid levels under stress conditions [1 - 2 1 . The study believes that Chinese medicine detoxification can comprehensively adjust and treat patients through the multi-target effect of traditional Chinese medicine compound, and can play a better adjustment role for complex, multi-system protracted withdrawal symptoms and prevention of relapse. Fuzheng Oral Liquid is a traditional Chinese medicine detoxification preparation. This paper observes its effect on the conditional position preference effect of drug dependent mice.

1 Materials and methods

1 . 1 animal

Kunming mice, male and female, female and male mice were kept in cages, body weight (2 2 ± 2 ) g

1 . 2 drugs

Fuzheng oral liquid (hereinafter referred to as Fuzheng). Hydrochloric acid drug injection

1. 3 instruments

The conditional position preference box consists of a shuttle box and a position preference video analysis system (infrared receiver system and computer data acquisition system). The outer box of the shuttle box is a dark box. The top of the shuttle box is provided with: a white light emitting device, an infrared tracking device and a ventilating fan; the inner box is a narrow rectangular box, the top is open, the box wall is smooth, and the barrier is divided into two boxes in the middle and respectively It is called black box and white box. There is a passage between the two boxes. The inner wall of the black box is black, and the bottom is rough. The inner wall of the white box is white and the bottom is smooth. Position preference video analysis system: The infrared tracking device monitors the activity of the experimental mice in the position preference box, and records the process in a video format on a computer. The software analyzes the animal's activity trajectory and records the animal's whiteness. Parameters such as box dwell time.

1.4 method

Experiments were carried out using a conditional position preference box, which was required to be carried out in a quiet environment. References [ 2 - 5 ] establish drug-dependent CPP and its regression and induction of recurrence.

1 . 4 . 1 Adapt to the environment

Before the experiment, the mice were placed in a shuttle box to adapt to the environment, and the mice were able to shuttle freely in the box for 5 do

1 . 4 . 2 pre-test phase

The white box residence time (in seconds) of a single mouse was determined using a conditional position preference box, once a day, continuously for 3 days, and averaged. We used a propensity experiment program to experiment with a white box with a mouse's non-habit preference. White box residence time: The residence time of the mouse in the white box within 1 5 minutes.

1 . 4 . 3 Training phase

A drug mental dependence model was established for 7 days. At 9 AM, the drug was injected subcutaneously by dose escalation. The dose of 7d was 20, 40, 60, 80, 100, 100, 100 m kg, and the mice after injection. Immediately put the white box (with the medicine box) and let it stay in the box for 60 minutes. 5 PM in the afternoon, subcutaneous injection of 0.9% sodium chloride injection, placed in a black box (non-contained kit), stayed in the box for 60 min o, thus allowing the mice to form a drug dependence and form new conditioning , from the preference for black boxes to prefer white boxes. The measurement was performed on days 1, 2, and 3 after the drug was stopped.

1 . 4 . 4 withdrawal period

The mice were placed in the shuttle box for free activity from the time of discontinuation of the drug for 12 days, and the white box residence time of the mice was determined for the last 3 days.

1 . 4 . 5 Animal grouping and administration

UP mice were randomly divided into normal saline group, drug group, and Fuzheng solution low, medium and high dose groups, with 10 groups in each group. The saline group was given subcutaneous injection of sodium chloride injection, the drug group was injected subcutaneously, and the group of Fuzheng solution was administered intragastrically at a dose of 1, 2, 4 m L / kg, and each group was administered for 5 days, twice a day ( 9 AM, 5 PM). On day 6, subcutaneous injection of hydrocortisone 5m g / kg induced relapse, and after 15 min, the mice were placed in a position preference box and the white box residence time was determined.

1.5. Statistical methods

The experimental data was expressed as (without soil:) and processed with the statistical software package SPS S10. 0, using factorial analysis of variance and t test.

2 results

2.1 The effect of drugs on the expression of UP in mice

The drug-trained mice showed preference for white boxes, and the white box residence time was significantly prolonged, with an average of (5 0 0. 3 2 1 0 4 .15) s, and shirt I! before training (2 1 0 . 8 4 There was a significant difference in soil 7 6 . 7 5 ) s, indicating that the drug-induced mouse CPP model was successfully established. After stopping the drug for a period of time, the CPP effect of the mice subsided, and the white box time was significantly shortened from (235.02±61.64) s to close to the drug training. Before, there was no difference between the two, and the white box after the drug training. There was a significant difference in residence time (P < 0.01). see picture 1

2. 2 Effect of Fuzheng Liquid on CPP Effect Induced by Nitride

The mice with the CPP effect subsided after the drug was stopped were randomly divided into different treatments. The white box time of each group of mice in each experimental stage is shown in Table 1. In the drug group, after the artificial drug relapse, the CPP effect was reappeared, and the white box residence time was significantly prolonged. The injection of hydrocortisone also induced the UP effect of the NS group mice, which showed a significant prolongation of the white box residence time. The three groups of mice treated with low, medium and high doses of Fuzheng solution inhibited the effect of hydrocortisone on CPP. The white box residence time of these three groups was significantly lower than that of the other two groups. Group comparisons were significantly different (P < 0.01). Moreover, it can be seen from the experimental data that the inhibition is dose-dependent, that is, the higher the dose of the righting solution in a certain dose range, the better the inhibition of the hydrocortisone-induced UP effect.

3 Discussion

The abuse of psychoactive drugs and the drug dependence of the drug-using population have always been medical and social issues of concern to human society. Conditional position preference (CPP) is a research method for research drug and psychotropic drug dependence established in the early 1980s. It is widely used because of its simplicity and reliable results (6 - 7 1 . From our experimental results It can be found that the drug can induce a stable C PP effect in mice with the drug kit, which proves that the drug can induce significant mental dependence in mice. Some studies suggest that the mice that form drug-dependent mice prefer the white box habit. About 12 days after stopping the drug, the black box is basically changed. However, the conditional preference of the white box (with the medicine box) can be maintained for about 30 days. It can be induced once there is effective stimulation [8 l . There are many types of stress stimuli. In animal experiments, forced swimming, electric shock, isolation, food restriction, etc. are often used. The common feature of stress is activation of the hypothalamic-pituitary-adrenal axis, which causes the adrenal gland to release glucocorticoids. Etc. [9] proposes that certain stress stimuli can enhance the self-administration behavior of opioids and induce the onset of drug addiction. Glucocorticoids are involved in the stress response of animals, thereby It evokes its UP behavior [ '. Ig. Exogenous glucocorticoids can enhance the release of dopamine in the ventral tegmental area (VTA) and nucleus accumbens (NA s ) of the midbrain, making the body stimulant or opioid Dependent behavior and psychological response, strengthen the conditional position preference of the drug in mice, and obtain similar results with stress [5 l. Our experiments also show that hydrocortisone can ignite the UP effect of mice.

In recent years, people have basically solved the problem of detoxification of western medicine, and then turned their attention to detoxification of traditional Chinese medicine. Studies have confirmed that Chinese herbal medicine can alleviate withdrawal symptoms, promote body recovery and increase appetite, and has great advantages and potential in protracted withdrawal symptoms against drugs, especially in relapse. The Fuzheng oral liquid used in this experiment is prepared from several kinds of Chinese herbal medicines such as Codonopsis pilosula and Gun Ginger. It has the functions of invigorating the kidney and strengthening the spleen, promoting qi and activating blood circulation, stopping diarrhea and relieving pain. It is used in the poisoning syndrome of opioid addiction and spleen. Kidney deficiency, blood stasis, inflammatory stagnation, shudder, chills, sputum, tears, sputum, fatigue, fatigue, lack of food, vomiting, diarrhea, severe pain, waist and knee pain, Yang disease nocturnal emission. In our previous experiments, we found that the drug actually resists the physical dependence of drug-dependent animals, that is, it can alleviate withdrawal symptoms, and then want to confirm whether it can fight mental dependence. In the experiment, different doses of Fuzheng solution can inhibit the recurrent UP effect induced by hydrocortisone. Therefore, it is believed that Fuzheng has anti-drug dependence. We envisage that the righting solution may affect the drug UP effect through the midbrain dopamine system, but this conclusion needs further research and direct data confirmation.

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