溴隐亭、培高利特、米非司酮、环磷酸亚胺对吗啡依赖性的影响

【作者】 牛海晨；

【导师】 程嘉艺；

【作者基本信息】 辽宁中医药大学 ， 药理学， 2007， 硕士

【摘要】 阿片类药物多次使用停药后出现一系列生理、心理依赖症状，此时脑内多巴胺能神经元功能低下，多巴胺（DA）递质含量降低。此时糖皮质激素含量增加，在吗啡强化过程中糖皮质激素与受体结合可以提高学习记忆能力，增强吗啡的奖赏效应。在戒断期间，糖皮质激素与受体结合可以增强生理依赖和负性情绪反应，诱导复吸的发生。实验中应用溴隐亭（D₂受体选择性激动剂）和培高利特（DA受体非选择性激动剂）提高多巴胺能神经元功能活性，缓解依赖症状。注射吗啡前，应用米非司酮抑制糖皮质激素与其受体结合，可以降低吗啡的奖赏作用，抑制学习记忆信息的获取，使成瘾强度降低。在戒断期间，应用米非司酮抑制糖皮质激素与其受体结合，可以缓解负性心理情绪和抑制环境线索诱发的戒断行为。初步探讨治疗吗啡依赖症状的药物治疗方法和成瘾的神经机制。实验结果表明D₂受体选择性激动剂溴隐亭能够明显抑制生理依赖症状，对心理依赖无明显抑制作用；DA受体非选择性激动剂培高利特能够抑制生理戒断症状和心理依赖行为。在吗啡强化的过程中，阻断糖皮质激素与受体结合可以抑制强化过程中学习记忆信息获取，在戒断期间阻断糖皮质激素与受体结合可以抑制戒断过程中学习记忆信息提取过程，同时实验数据表明环磷酸亚胺（CHX）阻断蛋白质合成可以在一定程度上抑制吗啡心理依赖。更多还原

【Abstract】 Opioids withdrawal syndromes included physical and psychological syndromes and at the same time the level of DA neurotransmitter in the brain was increased and function of DA neuron was decreased。But in the moment glucocorticoid can facility the effect of withdrawal syndromes so that being increased. In my experiment bromcriptine (D2 agonist) and pergolide (D1/D2 agonist)were used to increase the DA neuron function, pretreatment to morphine injection of UR486 can effectively decrease the reinforcement of morphine to inhibit the acquisition of memory information. During the withdrawal, treatment of RU486 can inhibit the extraction of memory information to decrease the negative mood and physical withdrawal, behaviors. These treatment is looking for a method to inhibit the withdrawal syndromes and explore the drug healing mechanisms. My result showed that bromocriptine can inhibit the physical withdrawal syndromes and pergolidecan do the psychological withdrawal syndromes and do the physical withdraw syndromes. And mifepristone can effectively inhibit acquisition and extraction of information. At the same time from some extent to say that CHX can inhibit synthesis of protein in the brain.更多还原