甘珀酸对小鼠吗啡依赖性位置偏爱的影响

摘要

Objective To investigate the effect of gap juction inhibitor carbenoxolone (CBX) on morphine addiction in mice. Methods Conditioned place preference (CPP) was established in ICR mice through prolonged morphine exposure. The influence of CBX on the acquisition or expression of CPP were observed through behavior test. Changes of the astrocytes were examined by immunofluorescence of glial fibrillary acidic protein (GFAP). Results ① Contrast to the control group, CPP was induced in the morphine-dependent group (P<0.05). ②CPP was inhibited significantly in the CBX-pretreated group (P<0.05), but not significantly in the CBX-treated group (P>0.05). The morphine may lead to increase of GFAP immunostaining in ventral tegmental area (VTA). ③ The GFAP immuno-reactive cells in CBX-pretreated group were fewer than those in morphine group. Conclusion CBX can suppress the acquisition of CPP induced by morphine, but the effect of CBX on the express of CPP was weak. CBX maybe play directly or by indirect effect of GFAP.%目的 探讨缝隙连接抑制剂甘珀酸(CBX)对小鼠吗啡成瘾的抑制作用.方法 将24只小鼠随机均分为生理盐水组、吗啡组、甘珀酸干预组和甘珀酸治疗组.进行条件性位置偏爱(CPP)测定,并作腹侧被盖区内星形胶质细胞标记物胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)免疫荧光染色.结果 条件反射训练后,吗啡组与生理盐水组相比,出现明显的位置偏爱效应 (P<0.05).在甘珀酸干预组,吗啡引起的小鼠位置偏爱行为受到显著抑制( P<0.05).甘珀酸治疗组,位置偏爱行为有所抑制,但与生理盐水组差异无显著性意义(P>0.05).吗啡组腹侧被盖区GFAP免疫反应强度明显高于生理盐水组; 而甘珀酸干预组GFAP的强度显著低于吗啡组.结论 甘珀酸能抑制吗啡依赖条件性位置偏爱的形成,而对条件性位置偏爱表达的作用较弱.机制可能与其阻断缝隙连接后继而降低胶质细胞GFAP的表达有关,也可能是阻断缝隙连接后的一个直接效应.