毒扁豆碱对吗啡导致的大鼠行为敏感化的抑制作用

PHYSOSTIGMINE BLOCKS BEHAVIORAL LOCOMOTOR SENSITIZATION INDUCED BY MORPHINE IN RATS

药物滥用导致的行为敏感化被认为与成瘾过程密切相关。本实验探讨吗啡导致的大鼠行为敏感化与神经递质乙酰胆碱的关系。实验动物分为3组,分别进行生理盐水、吗啡(10. 0mg/kg)、吗啡(10. 0mg/kg) +胆碱酯酶抑制剂毒扁豆碱(0. 2mg/kg)前处理, 36小时腹腔注射4次。前处理结束1周所有动物注射小剂量吗啡(4. 0mg/kg);使用生理盐水前处理的动物,第2周注射毒扁豆碱(0. 2mg/kg);使用吗啡前处理的动物,第2周注射小剂量吗啡+毒扁豆碱(0. 2mg/kg),第3周再次注射小剂量吗啡。动物每次接受注射后立即记录其在两小时内的活动量(10分钟为一个记录单元)。结果表明,毒扁豆碱既能够抑制吗啡诱导的行为敏感化,也能够阻断小剂量吗啡对行为敏感化的“点燃”作用。由此推论,吗啡导致的行为敏感化与其抑制乙酰胆碱分泌有关。

The long-term effects of repeated exposure to drugs of abuse are one of the central themes in drug addiction research. This study investigates the relationship between the behavioral locomotor sensitization induced by morphine and neurotransmitter acetylcholine. Rats were randomly assigned to two experimental groups and one control group receiving pretreatment, which were given four 10.0-mg/kg injections (i.p.) of morphine alone or with 0.2-mg/kg physostigmine or of saline alone over a 36 h period. At week 1 after pretreatment, all rats were challenged with 4.0-mg/kg morphine. Saline-pretreated rats received injection of physostigmine (0.2mg/kg) at week 2. Rats pretreated with morphine alone were challenged with 4.0-mg/kg morphine and 0.2-mg/kg physostigmine at week 2, and were challenged with 4.0-mg/kg morphine again at week 3. The results of this study showed that physostigmine could inhibit both development and expression of behavioral locomotor sensitization induced by morphine. In conclusion, these findings suggest that behavioral sensitization induced by morphine is related to inhibition of the central neurotransmitter acetylcholine release.