5-羟色胺5-HT2C受体激动剂抑制吗啡依赖小鼠纳洛酮诱导的戒断行为

摘要

Aim To explore the effect of pharmacolog-ical activation of serotonin 5-HT2C receptor (5-HT2C R) on naloxone-precipitated withdrawal in morphine-de-pendent mice. Method EthoVision Noldus video tracking system was used to record the effect of 5-HT2C R agonist WAY on locomotor activities and behavioral performances in mice.Results Selective 5-HT2C R ag-onist WAY (0.5,0.75 or 1 .0 mg·kg -1 ,i.p.)a-lone did not alter the locomotor activities as determined by distance traveled and velocity (all P values >0.05).Chronic morphine treatment induced depend-ence 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-pre-cipitated 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-HT2C R ameliorates naloxone-precipitated withdrawal symptoms in morphine-dependent mice.5-HT2C R may be a novel target to develop therapeutic ap-proach against morphine physical dependence,craving and relapsing.%目的：观察5-羟色胺2C 受体（5-HT2C R）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-HT2C R 在吗啡成瘾导致的躯体依赖中的作用。方法采用EthoVision 动物行为分析系统观察5-HT2C R 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、