可乐定脱毒治疗对吗啡依赖大鼠吗啡条件性位置偏爱效应和镇痛作用的影响

EFFECTS OF CLONIDINE TREATMENT DURING WITHDRAWAL ON CONDITIONED PLACE PREFERENCE AND ANALGESIA OF SUBSEQUENT MORPHINE IN RATS

目的:研究给予吗啡依赖大鼠可乐定治疗对吗啡奖赏效应和镇痛作用的影响。方法:采用剂量递增法(5-40mg·kg-1,每天3次,30d)建立吗啡依赖大鼠模型,在自然戒断后7d内给予可乐定(0.1mg·kg-1,每天3次)进行治疗;停用可乐定后训练大鼠吗啡(1mg·kg-1)条件性位置偏爱(CPP),观察CPP的形成速度和维持情况;期间利用热痛甩尾法,观察吗啡(5mg·kg-1)的镇痛作用。结果:CPP训练4d后,经可乐定治疗的大鼠形成了吗啡CPP,而未经可乐定治疗的大鼠没有形成CPP;经过8d训练后,经可乐定治疗及未治疗的大鼠均形成了明显的吗啡CPP;在训练停止后14d,经可乐定治疗大鼠的CPP已消退,而未经可乐定治疗的大鼠CPP没有消退。在镇痛实验中,可乐定治疗及未治疗大鼠应用吗啡前后的甩尾时间组间比较差异不显著。结论:可乐定治疗能改变吗啡依赖大鼠的吗啡奖赏效应,但不影响大鼠对吗啡镇痛作用的耐受。

Objective ： To investigate the effects of clonidine treatment on the reward and analgesia of subsequent morphine in rats. Methods ： Morphine dependence of rats was established by dose - increasing administration （5 - 40 mg· kg^-1 ,3 times ·d^- 1, for 30 d ）. During the initial 7 d of withdrawal, rats were treated with clonidine （0. 1 mg·kg^-1 ,3 times·d^-1 ）or saline. Then rats were trained for morphine （1 mg· kg^-1） conditioned place preference （CPP）. The acquisition and retention of CPP were monitored. Analgesia of morphine （5 mg· kg^-1） in rats was assayed with tail - flick protocol after CPP training. Results ：After 4 d training, clonindine -treated rats developed significant CPP, but non -treated rats did not. After 8 d training, both clonidine - treated and non - treated rats acquired significant CPP. After 14 d of training cessation, CPP of clonidine - treated rats extinguished, while CPP of clonidine non - treated rats still existed. Clonidine- treated rats and non -treated rats showed no significant difference in tail -flick test. Conclusion：Clonidine treatment during withdrawal affects the rewarding effects, but not the analgesia tolerance, to subsequent morphine exposure in morphine -dependent rats.