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Studies On New Anti-MS Drug: From New Animal Model To New Model Animal

Posted on:2008-01-03Degree:MasterType:Thesis
Country:ChinaCandidate:X H YuFull Text:PDF
GTID:2144360218458997Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Motion sickness (MS) is one of the most important problems in the field of space medicine. This disorder has been of interest to many investigators. The response, in terms of gastrointestinal and other peripheral changes, is characteristic of a general autonomic nervous disorder during MS. With the innovation of transport and industry in the last hundred years, more and more people suffer from MS because of the variety of motion environments (e.g., cars, boats, planes, tilting trains, funfair ride, space, and virtual reality). Therefore, the issue of MS protection and therapy should be solved in this area.Studies on the MS using common laboratory animals such as rats and mice are limited due to the lack of the ability to vomit. Pica, the consumption of a substance without nutritional value such as kaolin, can be induced in rats by various stimuli and in mice following exposure to rotation-induced hypergravity. So pica was used as an analogue to emesis in rats or mice in previous studies. But there exists dispute. In addition, it is an indirect observation and might be not sensitive enough. Therefore, it is essential to develop an animal model for MS in rats and mice. Here we propose a new experimental model for the evaluation of MS in rodents. In our preliminary study, it was found that, although lack of an emetic reaction, the rats presented several symptoms induced by rotation such as, piloerection, tremble, urinal and fecal incontinence. All these symptoms as well as emetic reaction are the manifestation of the disorder of autonomic nervous system in MS. Therefore, these symptoms may theoretically be taken as the parameters for MS in rodents in stead of emesis. Practically, the fecal granules of rats are easily to be scored and the existence of urinal incontinence, piloerection and tremble are easily determined. The present work was therefore designed to establish a new method for MS in rodents and to evaluate the anti-MS effects of a new combination drug in rats with this new method. In addition, the effects of rotation on kaolin intake were also observed in rats and mice in this study.The main study for the following three aspects:The novel screening methodlogy of anti-MS drug.1. The study on the new compound of anti-MS――Meidasuping.2. A novel mice animal model of MS.The main findings of this study are as followings:1. MS index in mice and rats are normal distribution. The MS index was significantly decreased in the mice treated with scopolamine at dose of 0.3 or 3.0 mg/kg. The MS index was significantly decreased in the rats treated with scopolamine at dose of 1.0 or 3.0 mg/kg. Rotation stimulus induced a slight but not significant increase in average kaolin intake in mice and rats.2. We did some experiments on the new compound with the above methods. The MS index was significantly decreased in the rats treated with Meidasuping at dose of 1mg/kg. The total activity, average speed, linearity is not different from the score in 5 minutes.3. We use the above method, we do a lot of experiment on mice and there is a difference in the sensitive to stimulate. We selected the mice of sensitive to stimulate to nurture offspring. After several generations of mice stimulated conditions for the faint of sensitivity has shown significant difference, and a significant difference in the trend of increase with each generation, we now have nurtured F8. In conclusion:1. This animal model is suitable for MS study in rats and mice2. The new compound Meidasuping might be a new method to treat or prevent MS. It shows a clear dose-effect relationship. The new compound not only has a anti-MS effect but also overcome the side effects such as drowsiness.3. According to the MS index of the mice, we selected the mice of sensitive to stimulate to nurture offspring. We conducted studies of protein research and morphological differences between physiological and pathological changes in the pathogenesis of motion sickness research and lay a good foundation for the prevention of motion sickness.
Keywords/Search Tags:motion sickness, animal model, scopolamine, modafinil, medasuping, rat, mice, kaolin, MS index
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