海洛因作用不同时程诱导大鼠CPP及海洛因依赖大鼠VTA区CREB磷酸化研究  

Differential duration of heroin action for induction of conditioned place preference and changes of CREB phosphorylation in the VTA of heroin dependent rat

作　　者：牛晨[1] 陈远寿[1] 潘贵书[1] 

机构地区：[1]遵义医学院生理教研室,遵义563000

出　　处：《神经解剖学杂志》2013年第3期329-332,共4页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金项目(30960109)

摘　　要：目的:观察不同时程注射海洛因对诱导大鼠条件位置偏爱(conditioned place preference,CPP)行为的影响及其海洛因依赖后大鼠VTA区CREB磷酸化的研究。方法:雄性SD大鼠32只(体重180～220 g),随机分为四组:海洛因依赖8 d组及其对照组,海洛因依赖10 d组及其对照组,每组8只。海洛因依赖组连续腹膜腔注射海洛因每日10 mg/kg,8 d和10 d,对照组注射等量的生理盐水,于训练结束的次日进行CPP检测。模型建立成功后,8 d组大鼠采用Western blot检测VTA区CREB磷酸化的表达。结果:(1)与相应的对照组比较,每日10mg/kg海洛因8、10 d组在伴药箱停留时间均明显延长(P<0.05),而两组大鼠在伴药箱停留时间比较差异无统计学意义。但8 d组更为省药、省时且大鼠无死亡。(2)与对照组比较,海洛因依赖8 d组大鼠VTA区CREB蛋白磷酸化增多(P<0.05)。结论:(1)两种时程均可成功建立大鼠CPP模型,但每日10 mg/kg海洛因8 d组建立的模型更为合适。(2)慢性海洛因给药大鼠VTA区CREB蛋白磷酸化增多。Objective： To observe the effects of different time-course of heroin injection on the behaviour of conditioned place preference （CPP） in rats and the change of expression of cAMP response element-binding protein （CREB） phosphorylation in the ventral tegmental area （VTA） of heroin dependent rats. Methods ： Thirty-two adult male Sprague-Dawley rats （180-220 g） were randomly divided into 4 groups （n = 8） ：8 days heroin dependent group and its control, and 10 days heroin dependent group and its control. The rats in heroin dependent groups received intraperiatoneal injections of heroin 10 mg/kg/d for 8 days and 10 days, respectively, to induce CPP. Normal saline was injected into rats of the control groups in the same way. The time spent in the drug-paired compartment was observed on the next day after last injecion and training for CPP. In 8 days heroin dependent group, the expression of phosphorylate CREB （P-CREB） in the ventral tegmental area was evaluated by using Western blot. Results： （1） Compared with the corresponding control groups, the time spent in the drug-paired compartments significantly increased in the groups receiving 10 mg/kg 8 d and 10 mg/kg 10 d （P 〈0.05）. However, there were no obvious differences between these two heroin dependent groups. It appears that, in 8 days heroin dependent group, less time consumption and less drug was required. In addition, there were no animal death in 8 days heroin dependent group. （2） In 8 days heroin dependent group, p-CREB level in the VTA was significantly increased than that in its control group. Conclusion ： （ 1 ） These two different time-course of heroin injections successfully induce the CPP model. But, the injections of heroin 10 mg/kg/d for 8 days is a more appropriate method to establish the CPP model; （2） Chronic treatment with heroin enhanced the CREB phosphorylation in rat VTA neurons.

关 键 词：条件位置偏爱模型 海洛因 CREB磷酸化 大鼠 

分 类 号：R749.6[医药卫生—神经病学与精神病学]