5-羟色胺5-HT_(2C)受体激动剂抑制吗啡依赖小鼠纳洛酮诱导的戒断行为  

Pharmacological activation of serotonin 5-HT_(2C) receptor ameliorates naloxone-precipitated withdrawal in morphine-dependent mice

作　　者：吴县 江勤[1] 庞刚[2] 刘欢[2,3] 陶欣荣[2,4] 董六一[1,2] 章功良[1,2] 

机构地区：[1]安徽医科大学药理学教研室,安徽淮南232001 [2]安徽医科大学药物成瘾研究所,安徽淮南232001 [3]安徽医科大学精神卫生临床学院,安徽合肥230032 [4]安徽理工大学,安徽淮南232001

出　　处：《中国药理学通报》2015年第4期518-523,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81271217;81470432;81471161);安徽省自然基金资助项目(No1408085MH174);安徽医科大学博士启动基金(No XJ201405)

摘　　要：目的观察5-羟色胺2C受体(5-HT2CR)激动剂WAY对吗啡依赖小鼠纳洛酮诱导戒断症状的防治作用,探讨5-HT2CR在吗啡成瘾导致的躯体依赖中的作用。方法采用Etho Vision动物行为分析系统观察5-HT2CR激动剂WAY对正常小鼠自发活动的影响;剂量递增法诱导小鼠吗啡依赖模型,观察WAY对吗啡依赖小鼠纳洛酮诱导戒断症状的影响。结果 WAY(0.5、0.75、1.0 mg·kg-1,i.p.)对小鼠自发活动没有明显影响。慢性吗啡诱导依赖小鼠运动距离、速度和跳跃等行为活动增加。WAY(0.5、0.75、1.0 mg·kg-1)和可乐定(0.2 mg·kg-1,i.p.)对吗啡依赖小鼠纳洛酮催促出现的打洞、跳跃、清理皮毛、站立、"湿狗"样抖动、摇头、清理脸部、抓挠戒断症状有明显的抑制作用(P<0.05)。结论药物激活5-HT2CR可明显的抑制吗啡依赖小鼠纳洛酮催促的戒断症状。5-HT2CR可能是潜在的治疗吗啡躯体依赖、渴求和复吸的靶点。Aim To explore the effect of pharmacological activation of serotonin 5-HT2Creceptor（ 5-HT2CR）on naloxone-precipitated withdrawal in morphine-dependent mice. Method Etho Vision Noldus video tracking system was used to record the effect of 5-HT2 C R agonist WAY on locomotor activities and behavioral performances in mice. Results Selective 5-HT2 CR agonist WAY（ 0. 5,0. 75 or 1. 0 mg ·kg^-1,i. p.） alone did not alter the locomotor activities as determined by distance traveled and velocity（ all P values 〉0. 05）. Chronic morphine treatment induced dependence in mice as demonstrated by increases in distance traveled,velocity and jumping behavior. WAY（ 0. 5,0. 75 or 1. 0 mg·kg^-1,i. p.） and clonidine（ 0. 2 mg·kg^-1,i. p.） significantly ameliorated naloxone-precipitated withdrawal symptoms,including burrowing,jumping,body grooming,rearing,＂wet dog＂shakes,head shakes,face grooming,penile grooming,scratch（ all P values〈 0. 05）. Conclusion Pharmacological activation of 5-HT2 CR ameliorates naloxone-precipitated withdrawal symptoms in morphine-dependent mice. 5-HT2 CR may be a novel target to develop therapeutic approach against morphine physical dependence,craving and relapsing.

关 键 词：5羟色胺 5HT2C受体 吗啡 依赖 纳洛酮 戒断症状 

分 类 号：R749.3[医药卫生—神经病学与精神病学]