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CCK-8S对谷氨酸神经递质系统介导的急性酒精依赖大鼠行为学作用及机制的研究
The Study of CCK-8S on Behavior and Its Mechanisms Included by Glutamat Meutrasmtw System in Acholoic Rats
【作者】 赵磊;
【作者基本信息】 石河子大学 , 病理学与病理生理学, 2011, 硕士
【摘要】 一、CCK-8S对急性酒精依赖大鼠的记忆与自主行为的影响目的:通过酒精依赖大鼠模型的建立,观察酒精对大鼠在记忆及自主行为方面的影响,以及给予CCK-8S后,酒精依赖大鼠在记忆及自主行为方面的变化,探讨CCK-8S对急性酒精依赖大鼠的记忆与自主行为影响的可能机制。方法:将实验动物随机分为11组(n=8):A组:10 ml/kg 0.9%生理盐水灌胃组;B组:10 ml/kg0.9%生理盐水灌胃与生理盐水腹腔注射组;C组:10 ml/kg 50%酒精灌胃组;D组:低剂量4μg/kg CCK-8S腹腔注射组;E组:低剂量4μg/kg CCK-8S腹腔注射与酒精灌胃组;F组:高剂量10μg/kg CCK-8S腹腔注射组;G组:高剂量10μg/kg CCK-8S腹腔注射组与酒精灌胃组;H组:CCK-8S阻断剂与低剂量CCK-8S腹腔注射及酒精灌胃组;Ⅰ组:CCK-8S阻断剂与高剂量CCK-8S腹腔注射及酒精灌胃组;J组:NMDA受体阻断剂腹腔注射组;K组:NMDA受体阻断剂腹腔注射与酒精灌胃组。观察大鼠在酒精摄入后的自主行为变化,采用水迷宫对大鼠在产生酒精依赖前后的记忆行为进行测试。结果: (1)大鼠在短期内摄入大量酒精后,其自主活动增加。(2)酒精依赖大鼠的水迷宫爬台测试时间延长200s以上。(3)给予CCK-8S后,可以减少急性酒精依赖大鼠的自主行为次数,缩短水迷宫爬台测试时间(P<0.05)。结论: CCK-8S能够减少急性酒精依赖大鼠的自主行为次数,并对其记忆改善有作用。二、CCK-8S对酒精依赖大鼠NMDA受体亚基在海马表达的影响目的:通过酒精依赖大鼠模型的建立,观察酒精对大鼠NMDA受体亚基在海马的表达影响,在记忆及自主行为方面的影响,以及给予CCK-8对大鼠NMDA受体亚基在海马的表达变化,探讨CCK-8S对急性酒精依赖大鼠NMDA受体亚基在海马的表达影响可能机制。方法:将实验动物随机分为11组(n=8):A组:10 ml/kg 0.9%生理盐水灌胃组;B组:10 ml/kg0.9%生理盐水灌胃与生理盐水腹腔注射组;C组:10 ml/kg 50%酒精灌胃组;D组:低剂量4μg/kg CCK-8S腹腔注射组;E组:低剂量4μg/kg CCK-8S腹腔注射与酒精灌胃组;F组:高剂量10μg/kg CCK-8S腹腔注射组;G组:高剂量10μg/kg CCK-8S腹腔注射组与酒精灌胃组:H组:CCK-8S阻断剂与低剂量CCK-8S腹腔注射及酒精灌胃组;Ⅰ组:CCK-8S阻断剂与高剂量CCK-8S腹腔注射及酒精灌胃组;J组:NMDA受体阻断剂腹腔注射组;K组:NMDA受体阻断剂腹腔注射与酒精灌胃组。经水迷宫实验对大鼠在产生酒精依赖前后的记忆行为测试后,取其海马组织,应用RT-PCR技术检测大鼠海马NMDA受体亚基mRNA的表达变化。结果: (1)酒精依赖大鼠NMDA受体(?)mRNA亚基在海马的表达较空白对照组大鼠增加。(2)给予CCK-8S后,酒精依赖大鼠NMDA受体mRNA亚基在海马的表达较空白对照组大鼠增加。(3)给予NMDA受体阻断剂后,酒精依赖大鼠NMDA受体mRNA亚基在海马的表达较空白对照组大鼠增加。结论: CCK-8S能够增加酒精依赖大鼠NMDA受体mRNA亚基在海马的表达。
【Abstract】 Ⅰ. The effects of CCK-8S on memory and voluntary behavior of acute ethanol induced rats.Objective: To establish ethanol induced rat model, we observed the effects of ethanol on memory and voluntary behavior of rats, the changes of memory and voluntary behavior after CCK-8S used in order to discuss the possible mechanism of the effects of CCK-8S on memory and voluntary behavior of acute ethanol induced rats.Methods: the rats were randomly divided into 11 groups (n=8):group A: 10 ml/kg 0.9% normal saline intragastric administration group; group B:10 ml/kg 0.9% normal saline intragastric administration+10 ml/kg 0.9% normal saline abdominal injection group; group C: 10 ml/kg 50% ethanol intragastric administration; group D:low-dose 4μg/kg CCK-8S abdominal injection: group E: low-dose 4μg/kg CCK-8S abdominal injection group+ethanol intragastric administration; group F: high-dose 10μg/kg CCK-8S abdominal injection; group G:high-dose 10μg/kg CCK-8S abdominal injection group+ethanol intragastric administration; group H: CCK-8S inhibitor and low-dose CCK-8S abdominal injection and ethanol intragastric administration group; group I: CCK-8S inhibitor and high-dose CCK-8S abdominal injection and ethanol intragastric administration group; group J:NMD A receptor inhibitor abdominal injection group; group K: NMDA receptor inhibitor abdominal injection and ethanol intragastric administration group; we observed the voluntary changes of rats after ethanol intake and tested the memory before and after ethanol dependence using water gaze method.Results: 1. the rats voluntary activities were increased after great amount of ethanol in short-term period with 200s; 2. the time of clamping of the rats were prolonged in ethanol induced rats; 3. the frequency of voluntary activities of acute ethanol induced rats were decreased and the time of clamping was shortened after using CCK-8S(P<0.05).Conclusions: CCK-8S can decrease the frequency of voluntary activities of acute ethanol rats and improve the memory.Ⅱ. The effects of CCK-8S on expression of NMDA receptor subunits in hippocampus of acute ethanol induced rats.Objective: To establish ethanol induced rat model, we observed the expression of NMDA receptor subunits in hippocampus, the changes of memory and voluntary behavior after CCK-8S used in order to discuss the possible mechanism of the expression of NMDA receptor subunits in hippocampus of acute ethanol induced rats.Methods: the rats were randomly divided into 11 groups (n=8):group A:10 ml/kg 0.9% normal saline intragastric administration group; group B:10 ml/kg 0.9% normal saline intragastric administration+10 ml/kg 0.9% normal saline abdominal injection group; group C:10 ml/kg 50% ethanol intragastric administration; group D:low-dose 4μg/kg CCK-8S abdominal injection: group E:low-dose 4μg/kg CCK-8S abdominal injection group+ethanol intragastric administration; group F: high-dose 10μg/kg CCK-8S abdominal injection; group G: high-dose 10μg/kg CCK-8S abdominal injection group+ethanol intragastric administration; group H:CCK-8S inhibitor and low-dose CCK-8S abdominal injection and ethanol intragastric administration group; groupⅠ: CCK-8S inhibitor and high-dose CCK-8S abdominal injection and ethanol intragastric administration group; group J: NMDA receptor inhibitor abdominal injection group; group K: NMDA receptor inhibitor abdominal injection and ethanol intragastric administration group; we tested the memory before and after ethanol dependence using water gaze method and then obtained the hippocampus tissue to detect the expression changes of mRNA of NMDA receptors by using RT-PCR technique.Results: 1. the expression of mRNA of NMDA receptors in hippocampus of ethanol induced rats was increased; 2. the expression of mRNA of NMDA receptors in hippocampus of ethanol induced rats was increased after using CCK-8S; 3. the expression of mRNA of NMDA receptors in hippocampus of ethanol induced rats was increased after NMDA receptor inhibitor administration.Conclusions: CCK-8S can increased the expression of mRNA of NMDA receptors in hippocampus of ethanol induced rats.
【Key words】 CCK-8S; ethanol dependence; NMDA receptor; memory; hippocampus; NMDA receptor subunits;