Cedemex re-addiction prevention ability research on Morphine addicted white mice

Dr.Lai Shu, Prof.PhD.Huang Renbin, Dr.Xie Haiyuan*

  Dr. Nguyen Phu Kieu, PhD**; Prof.PhD. Pham Kim Man**

  *China,Quangxi Nanning Medical university.

 ** Critical Diseases Research and Treatment Institute-Ha Noi-Viet Nam .

*Summary:

Target: Monitor and research to see if Cedemex is able to resist against mental reliance (good ability to prevent re-addiction).

 Method: Use conditional position likeness method to set up reliance model for Morphine and examine Cedemex reliance effect on white mice.

Result: White mice is taken Cedemex continuously for 5 days with 3 different dosages then taken Hydrocortisone to excite, white mice stay in white drawer (drawer with Cedemex), not last clearly, manner of experimental white mice likeness is not rehabilitated and return to  unconditional likeness status. With the group take Morphine, take salt water and the time of staying in white drawer is lasted longer, manner of liking white drawer on white mice is rehabilitate.

Conclusion:Cedemex is able to resist against mental reliance (good ability to prevent re addiction)

Keywords:

Morphine, Cedemex, addiction, conditional position likeness, re-addiction prevention.

Many experimental research show that the addiction shape due to addictive substance influence to nerve excitement central is chronic process, a recrudesced disease. Because of nerve system structure and function manifest changes. Opium addiction and addictive substances is a concerning matter of society and medicine. They manifest on 2 aspects: practical addiction (physiological addiction) and metal reliance (psychological addiction). Physiological addiction manifest the appearance of drug hunger like observable preclinical therapy. Some effective medicines may be taken instead to overcome drug hunger status, but psychological addiction or metal reliance manifest after drug hunger stage, addicts’ demand must have drug. Partly addicts cannot suffer from shortage of drug so that they are easy to re-addiction. For psychological addiction, traditional drug detoxification methods are not effectively. According to assessment, among of detoxification addicts, the rate of re-addiction is 90%.

Drug demand (hunger for drug) and re-addiction manner are closed to memory activation and concentration of Glycocorticoides group after excitement satisfaction. White mice after Morphine addiction will generate available position likeness changes, will enjoy Morphine usage position (although it is not the right drawer). Through fixed time of 9 days, the character of Morphine drawer will disappear. But if taking  Hydrocortisone (5mg/kg weight, skin injection), it causes to take Morphine drawer again. This is made us to recognize that white mice are re-addicted. Our experiment result show that Cedemex may prevent re-addiction when taking Hydrocortisone and activate the character of Morphine drawer on white mice.

*Research materials:

1. Cedemex, capsule 500mg, made by Critical Diseases Research and Treatment Institute, Nalotone chlohydrate is made by Chich Kieu Pharmacy company, Hunan under code no: 20040706, Morphine chlohydrate is made by Tham Duong no1 Pharmacy factory under no: 20040402.

2.White mice, Kunming purebred breeder, male and female divide into half each(distinguishdifferent cages to avoid copulated mice leading pregnancy that will change weight during experimental process), average weight is 20-24gram that is provided by Quangxi medical university experimental animals feeding center.

3.Equipments: Position likeness experimental sideboard has 2 compartments, rectangular. Color of 2 compartments is different, choosing black and white color, the surrounding edges are plain, bottom of each compartment are one plain and one rough. Two compartments are reamed out. One computer is connected to 2 compartments to monitor the circulation and residence of mice, record and analyze the result. The equipment is provided by ShangHai, Cat Luong Microsoft  Science and Technology company.  

*Experimental method:

1. Psychological reliance experimental model with Morphine on white mice.

Using conditional position likeness method to carry out analyzing in silent environment. Firstly, choosing white mice, put chosen mice into 2 black and white reamed out  drawers and record time, put surveying mice with black drawer then record time of its staying for about 15 minutes, experiment continuously for 3 days. Choosing all black liking mice for experiment, black is mice likeness. All chosen mice are divided into natural groups. Everyday at eight o’clock, inject into skin Morphine according to raising concentration: 20mg/kg, 40mg/kg, 60mg/kg, 80mg/kg, 100mg/kg, 100mg/kg, 100mg/kg continuously for 7 days, After each Morphine injection, immediately put mice into white drawer of experimental compartment (drawer with Morphine) for about 60 minutes. In the afternoon at 4, inject skin with salt water solution and quickly put them into black drawer for about 60 minutes. Mice in white drawer through Morphine injection process will gradually change position likeness into white drawer (unnatural position likeness drawer), so mice have taken form of psychological Morphine addiction. On 8^th, 9^th and 10^th day (stop giving Morphine the 1^st ,2^nd and 3^rd day), put each mouse into experimental compartment, don’t need to monitor for first 5 minutes then record next 15 minutes of staying time of mice in black drawer. After that, monitor every other day until mice return to initially natural position likeness (the time of mice stay in black drawer like before giving Morphine).

2        Mice Subgroup and give Morphine.

For Morphine addicted mice, after not giving Morphine for 9 days, manner of white drawer likeness (Morphine given drawer) will gradually disappear. This time we divide mice into 5 groups: Control group (negative group), Morphine usage group (positive group), small, medium and big dosage Cedemex usage groups, 10 mice each group. Continuously for 5 days, 2 times/day salt water solution injection for control group, positive group is given Cedemex, other groups are given Cedemex designated dosage. From 6^th day, after skin injection with Hydrocortisone for 15 minutes, put mice into experimental compartment, black and white drawers are reamed out. Surveying mice of black drawer is about 5 minutes then start recording mice staying time in black drawer.

3        Statistics data processing.

Use SPSS to process data, average value (x±s) to display, compare each group with test

*Experimental result:

All mice group after being addiction caused with Morphine, the average time in black drawer reduced, that is confirmed mice are affected white drawer likeness manner or mice become Morphine addicted, see table 1.

For Cedemex average and big dosage group, after excited with Hydrocortisone, average time in black drawer compared before giving Morphine and Cedemex has no differences with statistics significance. But comparison after Morphine injected, average time in black drawer has differences with statistics significance. This is proved that with 2 kind of Cedemex dosages that rejects mice white drawer likeness manner. Clearly, Cedemex is able to resist mental reliance (psychological addiction) on mice with Morphine (good effect in preventing re-addiction), see table 1.

For Cedemex small dosage group, after excited with Hydrocortisone, average time in black drawer compared before giving Cedemex has no differences with statistics significance. But comparison before Morphine injected, the time in black drawer has differences with statistics significance. This is proved that with small dosage of Cedemex that rejects mice white drawer likeness manner. In the other hand,  Cedemex small dosage is also able to resist mental reliance (psychological addiction) on mice with Morphine (good effect in preventing re-addiction).

With Morphine usage mice group after excited with Hydrocortisone, average time in black drawer compared before giving Morphine have clear differences with statistics significance. But comparison after Morphine injected, the time in black drawer has no differences with statistics significance. This is proved that Hydrocortisone has no effect to reject mice white drawer likeness manner, see table 1.     

With salt water usage mice group after excited with Hydrocortisone, average time in black drawer compared before giving Morphine and Cedemex have no differences with statistics significance. But comparison after Morphine injected, the time in black drawer has no differences with statistics significance. This is proved that with salt water cannot reject mice white drawer likeness manner after Morphine addicted, and Hydrocortisone direct Morphine addicted mice white likeness manner, that can cause re-addiction for mice, see table 1.

Table 1: Average time (counted with second) in mice groups black drawer (x±s,n=10)

Compare after giving Morphine: ***p<0.001

Compare after giving Hydrocortisone: #p<0.05

Compare before giving Morphine and before continue giving Morphine: °°°p<0.001

Compare before giving and before giving physiological salt water: ×××p<0.001

Note: With 3 Cedemex dosages, Morphine and physiological salt water groups before giving Hydrocortisone, use Cedemex, Morphine and physiological salt water.

*Comment and conclusion:

For recent years, conditional likeness experiment is an effect method used widely to evaluate medicine mental reliance. After causing Morphine addiction with training of conditional likeness manner, keep taking medicine for 30 continuous days and use re-addiction excitement measurement. There are a lot of re-addiction excitement methods, in experimental animal model, normally use compel: swimming, electric shock, isolate, food limit…Excitements general characteristics are to activate brain lower endocrine-Tung gland-suprarenal skin (HPA), cause suprarenal gland to generate Glycocorticoides. Alien source excite suprarenal skin to enhance production and release Dopamine from brain central (VTA and NAs area), make body has physiological reaction and reliance manner with addictive mental likeness substance excitement or opium and opium derivative. Make mice become conditional position likeness manner and similar likeness changing situation.

The above experimental result may prove Hydrocortisone to direct white mice generate Morphine re-addicted manner, Cedemex is able to prevent Morphine of experimental mice.

In summary, with the method of using black and white compartments to experiment white mice position likeness manner, we conclude that: Morphine, Hydrocortisone can set up re-addiction manner model; Cedemex is able to prevent re-addiction on white mice.