噻诺啡灌胃给药对小鼠甲基苯丙胺行为敏化的影响

EFFECTS OF INTRAGASTRIC ADMINISTRATION WITH THENORPHINE ON METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION IN MICE

目的:探讨新型丁丙诺啡同系物-噻诺啡,灌胃(ig)给药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ig噻诺啡对小鼠的自主活动及单次给予甲基苯丙胺所诱导的小鼠高活动性的影响。建立甲基苯丙胺诱导的小鼠行为敏化模型,观察噻诺啡对行为敏化形成、转化及表达的影响。结果:(1)单次ig噻诺啡(1 2 5 - 5 0mg·kg-1)可剂量依赖性地抑制小鼠的自主活动(P <0 . 0 1) ,其作用多次给药后产生耐受;(2 )噻诺啡对单次给予甲基苯丙胺所诱导的小鼠的高活动性无明显影响;(3)噻诺啡对甲基苯丙胺诱导小鼠行为敏化的形成和表达无明显作用,却可显著抑制敏化的转化过程(P <0 . 0 5 )。结论:ig噻诺啡可抑制小鼠中枢神经系统,阻断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 (Then), a new buprenorphine analogy, on the process of methamphetamine (MA)-induced behavioral sensitization in mice. Methods: Locomotor activity was detected after administration with Then or co-administration of Then with MA in mice. Mice were induced behavioral sensitization to MA, and administered with the combination of MA and Then to observe the effects of Then on the development, transfer and expression of behavioral sensitization to MA. Results: (1) A single intragastric administration of Then (1.25-5.0 mg·kg -1) could dose-dependently inhibit the locomotor activity in mice (P<0.01) and the effects of Then on locomotor activity developed tolerance after repeated administration; (2)Co-administration of Then couldn't suppress the hyperactivity induced by a single administration of MA in mice; (3) Although Then couldn't inhibit the development and expression of MA-induced behavioral sensitization, it could significantly inhibit the transfer of behavioral sensitization to MA in mice (P<0.05). Conclusion: Then can suppress the central nervous system and the transfer of MA-induced behavioral sensitization in mice, suggesting that Then may have the effect of interfering MA produced addiction.