甲氧氯普胺对吗啡依赖性的影响

EFFECTS OF METOCLOPRAMIDE ON MORPHINE DEPENDENCE

目的:观察甲氧氯普胺对离体豚鼠回肠吗啡戒断收缩和吗啡精神依赖性的影响。方法:离休豚鼠回肠吗啡戒断收缩实验和吗啡诱导小鼠位置偏爱实验。结果:(1)离休豚鼠回肠吗啡依赖实验显示:250-500μmol·L^(-1)甲氧氯普胺可显著抑制离体豚鼠回肠吗啡依赖的形成和纳洛酮促发的戒断收缩,作用呈剂量依赖性;(2)甲氧氯普胺的剂量大于10(10-40)mg·kg^(-1)(ip),可有效抑制吗啡诱导的小鼠条件性位置偏爱的形成,而其本身并不造成位置厌恶。结论:甲氧氯普胺对吗啡身体依赖的形成、戒断症状以及精神依赖的形成均有一定的抑制作用。

Objective: To study the effects of metoclopramide (Meto) on morpinne physical and psycinc dependence. Methods: Isolated guinea - pig ileums were incubated with morpinne hydrochloride to produce dependence. Withdrawal contractions were precipitated by naloxone. Different doses of Meto were given either at the same time with the administration of morpinne before or after the model established. Effect of Meto on psycinc dependence of morpinne was examined through conditioned place preference( GPP). Results: Meto (250, 500 jumol L-1) significantly ininbited the contraction of morpinne dependent isolated guinea - pig ileum dose - dependently, both administered 30 min prior to the precipitation of naloxone and given at the same time of incubation of morpinne. Meto (10-40 mg kg-1 d-1, ip) could successfully prevent the development of GPP induced by morpinne without producing the effect of place aversion itself (40 mg kg-1 d-1). Conclusion: Meto can ininbit the development of morpinne dependence in naive isolated guinea - pig ileum and withdrawal contraction precipitated by naloxone in isolated morpinne - dependent guinea - pig ileum significantly and dose - dependently. Also it can prevent the development of CPP induced by morpinne in mice.