中缝背核参与大鼠吗啡依赖和戒断的形成机制研究  

Study on the mechanism of dorsal raphe nucleus to participate in the development of morphine dependence and withdrawal in rat

作　　者：秦承伟[1] 张勇[1] 赵彦明[1] 高桃[1] 张如意[1] 张励才[2] 

机构地区：[1]滨州医学院附属医院麻醉科,山东滨州256603 [2]徐州医学院麻醉学院,江苏徐州221002

出　　处：《中国临床药理学杂志》2011年第10期785-788,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察大鼠脑内神经核団中缝背核(DRN)在一氧化氮(NO)介导的吗啡依赖和戒断形成的作用机制。方法雄性成年SD大鼠随机分为5组:戒断组(腹腔注射吗啡+纳洛酮);依赖组(注射吗啡+生理盐水);生理盐水组(注射生理盐水);纳洛酮组(注射生理盐水+纳洛酮);抑制剂组(注射吗啡加NOS抑制剂+纳洛酮)。戒断组和依赖组,用剂量递增法经腹腔注射吗啡10～100mg.kg-1,每天3次,连续5天,建立吗啡依赖与戒断模型,并进行行为学观测与评分后,用神经元型一氧化氮合酶(nNOS)免疫组织化学标记,计数各组动物相同层面脑片上nNOS标记细胞的表达情况。结果戒断组,戒断症状及总评分较对照组和依赖组均差异显著(P<0.01);NOS抑制剂组,戒断症状评分较戒断组明显降低(P<0.05)。于中缝背核相应区域计数到部分nNOS标记神经元,生理盐水组及纳洛酮组比较无显著性差异;而依赖组与戒断组,其神经元计数明显增加(P<0.05);而NOS抑制剂组,神经元数量较戒断组明显减少(P<0.05)。结论脑内中缝背核可能通过一氧化氮信号通路参与了大鼠吗啡依赖与戒断的形成。Objective To observe the effect of the dorsal raphe nucleus（DRN） of rat brain parenchyma in the development of morphine dependence and withdrawal by nitric oxide（NO） mediation.Methods Male adult Sprague-Dawley rats were divided randomly into 5 groups： withdrawal（morphine ＋ naloxone） group,dependence（morphine＋saline） group,saline（saline） group,naloxone（saline ＋ naloxone） group and L-NAME（morphine＋naloxone＋L-NAME） group.All animals were killed and the relative tissue of rats′ brain was removed after the ethology surveying and the scoring of withdrawal symptoms.Frozen serial coronal sections were cut.Then neuron nitric oxide synthase（nNOS） was marked by immunohistochemistry.The number of the nNOS positive neurons on the same segmental brain sections were counted.Results The withdrawal symptoms of the withdrawal group were significant.Scores of all signs were significantly higher than the dependence group and control groups（P〈0.01）.The withdrawal signs of L-NAME group attenuated obviously compared to that of withdrawal group（P〈0.05）.There was no significant difference in the number of nNOS labeled neurons of saline and naloxone group.The number of nNOS labeled neurons of dependence and withdrawal group increased significantly compared to those of the above groups（P〈0.05）.The number of nNOS labeled neurons of L-NAME（L-nitro-arginine-methyl-ester） group was decreased significantly compared to that of withdrawal group（P〈0.05）.Conclusion DRN of rat brain parenchyma might partly be participated in the development of morphine dependence and naloxone precipitated withdrawal by NO signal passageway.

关 键 词：中缝背核 吗啡 戒断 一氧化氮合酶 

分 类 号：R965.1[医药卫生—药理学] R971.1[医药卫生—药学]