青风藤及青藤碱对吗啡依赖小鼠位置偏爱效应和脑内组胺水平的影响

目的探讨中药青风藤及其有效成分青藤碱对吗啡诱导的小鼠条件性位置偏爱(CPP)及脑内组胺(HA)水平的影响。方法采用位置偏爱箱法,连续皮下注射吗啡(9mg/kg·b.w.)6d,引起小鼠产生显著的条件性位置偏爱效应。实验分空白对照组、吗啡模型组(9mg/kg·b.w.)、青风藤醇提液组(10g/kg·b.w.)、青藤碱组(60mg/kg·b.w.)、苯海拉明组(30mg/kg·b.w.)、CP48/80组(5mg/kg·b.w.)和L-组氨酸组(750mg/kg·b.w.),后5个给药组分别在位置偏爱训练的第4天开始给药,连续用药3d。脑内组胺含量采用荧光分光光度法测定。本实验同时检测青风藤、青藤碱、苯海拉明、CP48/80及L-组氨酸对小鼠的奖赏效应或厌恶效应。结果吗啡模型组小鼠在伴药箱中停留的时间明显延长,小鼠脑内HA水平显著升高(P<0.01)。青风藤或青藤碱连续用药可显著抑制吗啡引起的小鼠位置偏爱的形成,降低脑内的HA含量。青风藤、青藤碱及L-组氮酸对正常小鼠脑内组脑水平有升高作用(P<0.01),但3药本身并不使小鼠产生奖赏或厌恶效应。CP48/80能使正常及吗啡依赖小鼠脑内组胺含量明显减少(P<0.01),但该药对CPP无明显影响。结论吗啡诱导的小鼠位置偏爱效应与脑内HA水平升高、中枢组胺能神经系统激活有关。青风藤及青藤碱能消除吗啡诱导的小鼠条件性位置偏爱的形成,对脑内组胺水平的改变具有调节作用。

Effects of Caulis Sinomenii and sinomenine on morphine-induced place preference and brain histamine level in mice

Objective To evaluate the effects of Caulis Sinomenii and sinomenine on conditioned place preference(CPP)induced by morphine and brain histamine level in mice.Methods Sixty mice were randomized into 6 equal groups and morphine(Mor)was injected subcutaneously(9 mg/kg)for 6 consecutive days to induce CPP using a shuttle box.Since the 4th day of training,the mice in 5 of the groups were treated for 3 consecutive days with Caulis Sinomenii(10 g/kg),sinomenine(60 mg/kg),diphenhydramine(30 mg/kg),CP48/80(5 mg/kg)and L-histidine(750 mg/kg)in addition to morphine(9 mg/kg)treatment,respectively,leaving the other group with exclusive morphine treatment.Another 10 mice received saline injection to serve as saline control group.The content of histamine(HA)in the mouse brain was measured by fluorospectrophotometry.Results In morphine group,the mice showed significantly extended stay in morphine-paired compartment whose HA content in the brain was markedly increased(P<0.01).Treatment with Caulis Sinomenii and sinomenine resulted in significantly reduced time of stay in morphine-paired compartment and brain HA level(P<0.01).Conclusion CPP induced by morphine in mice is associated with increased HA level in the brain.Caulis Sinomenii and sinomenine can suppress the acquisition of place preference induced by morphine and modulate HA level in the central nervous system in morphine-dependent mice.