N-nitro-L-arginine Attenuates Morphine and Dihydroetorphine-induced Place Preference in Mice  

N-硝基-L-精氨酸抗吗啡、二氢埃托啡诱导小鼠位置偏爱作用(英文)

作　　者：万兴旺[1] 黄矛[2] 何雅琴[1] 李万亥[3] 万莉[4] 由振东[5] 路长林[5] 

机构地区：[1]第二军医大学东方肝胆外科医院国际合作生物信号转导研究中心,上海200438 [2]第二军医大学基础医学部新药评价中心,上海200433 [3]第二军医大学药学院药理教研室,上海200433 [4]第二军医大学长海医院药学部,上海200433 [5]第二军医大学基础医学部神经生物学教研室,上海200433

出　　处：《Journal of Chinese Pharmaceutical Sciences》2002年第4期162-165,共4页中国药学（英文版）

基　　金：ThisprojectwassupportedbyGrantofthePLALaboratoryforNewDrugEvaluation (No .96-0 2 )

摘　　要：Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demonstrates that opiate psychical dependence is aproblem more troublesome. It has been reported that acute and chronic administration of L- NNA canmarkedly retard the development of tolerance to physical dependence on morphine, and suppress theabstinence syndromes precipitated by naloxone in opiate dependent rodents, and even reverse theexisting morphine tolerance. However, the effect of L-NNA on the positive reinforcement ofpsychically active substances and its possible mechanism have not yet been reported. In presentstudy, the effect of L- NNA en the psychical dependence induced by opiates was evaluated on thebasis of conditioned place preference.采用条件性位置偏爱模型对N 硝基 L 精氨酸 (L NNA)在吗啡、二氢埃托啡精神依赖中的作用进行了研究。L NNA 5mg·kg-1可使吗啡、二氢埃托啡精神依赖小鼠在条件性位置偏爱箱偏爱侧停留时间分别从 6 0 9± 2 0 2min ,7 98± 0 72min显著增加到 9 31± 1 10min (P <0 0 1) ,9 4 8± 1 2 1min (P <0 0 1)。小鼠皮下注射吗啡、二氢埃托啡形成精神依赖后 ,脑内NO含量升高至 (46 3 3± 18 6 )pmol·mg-1蛋白、(470 9± 16 4 )pmol·mg-1蛋白 ,显著高于生理盐水组的 (40 7 9± 15 6 )pmol·mg-1蛋白水平 (P <0 0 1)。而连续协同给予L NNA 5mg·kg-1三天后 ,吗啡、二氢埃托啡精神依赖小鼠脑内NO的含量分别降低至 (40 3 5± 17 2 )pmol·mg-1蛋白 (P <0 0 1) ,(412 2± 2 3 8)pmol·mg-1蛋白 (P <0 0 1) ,显著低于给予L NNA前的水平。与生理盐水组小鼠水平无显著性差异。我们的结果表明 :L NNA可逆转吗啡、二氢埃托啡所致的精神依赖 ,L

关 键 词：Psychical dependence MORPHINE Dihydroetrophine Nitric oxide 

分 类 号：R965[医药卫生—药理学]