噻诺啡对小鼠甲基苯丙胺行为敏化的影响

Effects of thenorphine on methamphetamine-induced behavioral sensitization in mice

目的:探讨新型阿片受体部分激动剂-噻诺啡对小鼠甲基苯丙胺行为敏化过程的影响。方法:测定小鼠的自主活动,观察噻诺啡对小鼠的自主活动及急性甲基苯丙胺处理所致小鼠活动增强效应的影响。小鼠腹泻注射甲基苯丙胺2mg·kg^(-1)·d^(-1),连续7d,建立甲基苯丙胺诱导的小鼠行为敏化模型,观察噻诺啡对小鼠行为敏化的影响。结果:单次皮下注射噻诺啡(0.0625～1.0mg·kg^(-1))可剂量依赖性地抑制小鼠的自主活动(P<0.05),连续给药7d,噻诺啡对小鼠自主活动的抑制作用不产生敏化,而耐受。噻诺啡对急性甲基苯丙胺处理所致小鼠的高活动性无明显影响。噻诺啡对甲基苯丙胺诱导的小鼠行为敏化的形成和表达无显著作用,但可剂量依赖性地抑制敏化的转化(P<0.05或P<0.01)。结论:噻诺啡对中枢神经系统具有抑制作用,并且可以阻止甲基苯丙胺诱导小鼠产生行为敏化的转化过程,提示噻诺啡可能对甲基苯丙胺的成瘾行为具有一定的干预作用。

Objective:To investigate the effects of thenorphine,a new partial agonist of opiatereceptors,on the process of methamphetamine (MA)-induced behavioral sensitization in mice.Meth-ods:Locomotor activity was detected after administration with thenorphine or co-administration ofthenorphine with MA in mice.Mice were induced behavioral sensitization to MA by intraperitoneal in-jection of 2mg·kg^(-1) MA once daily for 7 days,and administered with the combination of MA andthenorphine to observe the effects of thenorphine on behavioral sensitization to MA.Results:A singleadministration of thenorphine (0.0625～1.0mg·kg^(-1)) could dose-dependently inhibit the locomotoractivity in mice (P<0.05) and the effects of thenorphine on locomotor activity developed tolerance,instead of sensitization after repeated administration.Co-administration of thenorphine couldn't inhibitthe MA -induced hyperactivity in mice.Although thenorphine couldn't inhibit the development andexpression of MA sensitization,it could dose-dependently suppress the transfer of MA sensitization(P<0.05 or P<0.01).Conclusions:Thenorphine could suppress the central nervous system and thetransfer of MA sensitization in mice,suggesting that thenorphine may be effective against the addictionof MA.