吗啡诱导CPP建立和消退大鼠海马CA1区超微结构变化的研究

Ultrastructural Changes in Hippocampal CA1 during Morphine Induced Conditioned Place Preference Establishment and Extinction in Rats

目的比较吗啡(morphine,mor)诱导的条件性位置偏爱(conditioned place preference,CPP)建立和消退阶段大鼠海马CA1区超微结构的变化,揭示海马CA1区超微结构的变化与CPP建立和消退过程的关系.方法恒量法(10 mg/kg)连续颈背部皮下注射(subcutaneous,SC)吗啡8 d建立吗啡依赖大鼠CPP模型;用生理盐水替代吗啡训练大鼠10 d,使形成的CPP逐渐消退.应用透射电镜动态观测吗啡CPP建立和消退大鼠海马CA1区超微结构的变化.结果 10 mg/kg吗啡8 d诱导CPP建立,生理盐水训练10 d可以成功消退CPP;CPP建立阶段海马CA1区超微结构以变性和坏死为主,主要表现为胞浆肿胀,粗面内质网扩张,线粒体肿胀、溶解,细胞固缩等;消退阶段超微结构以坏死和凋亡为主,主要表现为细胞核固缩、胞浆肿胀、电子致密度增高,细胞器、细胞膜溶解,内质网池形成,细胞核常染色质浓聚、边集,核周隙增大等.结论海马CA1区神经元发生不可逆的损害,此变化可能与吗啡精神依赖有关.

Objective To compare the ultrastructural changes in hippocampal CA1 during morphine induced conditioned place preference establishment and extinction in rats,and to elucidate the relation between the ultrastructural changes and the progress of conditioned place preference.Methods Morphine was administered via subcutaneous injection at constant dose（10 mg/kg）for 8 d to establish morphine CPP.The rats were given 10 d saline extinction training to extinguish CPP.The changes of ultrastructures in hippocampus during morphine induced conditioned place preference establishment and extinction in rats were observed dynamically by using transimission electron microscope.Results Injecting morphine（10 mg/kg）for 8 d succeeded to produce CPP.After 10 days training with saline,CPP failed to be induced.Ultrastructure of CPP establishment displayed degeneration and necrosis mainly,such as endochylema swelling,rough endoplasmic reticulum（RER）extension,mitochondria swelling and solution,cell pyknosis and so on.Ultrastructure of CPP extinction reflected necrosis and apoptosis mainly,such as karyopyknosis,endochylema swelling and electro-dense raised up,organelle and cell membrane solution,endoplasmic reticulum cisterna formation,karyon euchromatin thickening and margination,perinuclear cisterna augmentation and so on.Conclusion The inreversible damage have taken place in hippocampal CA1 neurons,and this change may be related to morphine psychological dependence.