一氧化氮合酶抑制剂L-NAME对吗啡依赖小鼠位置偏爱及戒断症状的影响  

The effects of L-NAME, an inhibitor of NOS on CPP and withdrawal symptoms in morphine-dependent mice

作　　者：姜美俊[1] 刘学兵 苏中华[3] 谌红献[4] 郝伟[4] 

机构地区：[1]广东省人民医院 [2]广东省佛山市顺德区伍仲珮纪念医院 [3]山东省济宁市精神病防治院 [4]中南大学湘雅二医院精神卫生研究所

出　　处：《中国行为医学科学》2006年第2期99-101,共3页Chinese Journal of Behavioral Medical Science

基　　金：国家重点基础研究项目(2003CB515400);国家自然科学基金(30370522)

摘　　要：目的探讨一氧化氮合酶抑制剂L-NAME在吗啡依赖及其戒断症状中的作用,为临床干预提供依据。方法吗啡腹腔注射制造小鼠吗啡依赖模型,剂量从10mg.kg-1.次-1逐日递增至第7天时70mg.kg-1.次-1;L-NAME和纳洛酮同期干预,每次吗啡注射前5min,分别皮下注射纳洛酮1mg.kg-1.次-1和L-NAME2mg.kg-1.次-1,观察小鼠位置偏爱(CPP)产生情况。用药1周后皮下注射纳洛酮催瘾,观察戒断后小鼠的戒断体征,生理盐水作为空白对照。结果实验组小鼠在吗啡腹腔注射1周后产生了CPP[(457±304)s,F=7.967,P<0.01];吗啡注射同时给予L-NAME干预阻止了吗啡依赖的形成[CPP(148±108)s],并且减轻了吗啡戒断时的戒断体征跳跃次数减少[(18.40±22.61)次]、体质量丧失增加[(0.25±0.07)g],起跳潜伏期缩短[(14.10±11.29)min]、直立次数增加[(4.87±1.74)次]、躯体拉伸次数增加[(1.52±1.34)g]、腹泻加重[(0.38±0.48)次]。结论L-NAME能有效对抗吗啡所致的小鼠吗啡依赖,并且能有效减轻吗啡撤药时戒断体征的表达。Objective To explore the effects of L-NAME to morphine dependence and withdrawal syndrome in mice. Method All mice were divided into 3 groups. Morphine （The doses varied from 10mg·kg^-1. time^-1 to final 70mg.kg^-1. time^-1 ）, morphine plus L-NAME （ with the dosage of 2mg. kg^-1. time^-1 ） and saline were injected intraperitonally representatively, After each injection, behavioral observation was recorded. One week later naloxone was injected intraperitonally to precipitate the withdrawal symptoms. CPP and withdrawal symptoms were compared between different groups. Results CPP in experimental group was statistically prolonged than the control after 1 week＇s injection of morphine（ F =7. 967, P〈0.01 ）. Withdrawal symptoms were significantly reduced by L-NAME when naloxone was given （ P varied from 0. 000 to 0.05 ）. Conclusion L-NAME can prevent the development of morphine dependence in mice and induce the expression of withdrawal symptoms.

关 键 词：L-NAME 吗啡依赖 位置偏爱 戒断症状 

分 类 号：R749.64[医药卫生—神经病学与精神病学]