影响吗啡动物行为效应的因素及其机制
陈晶
学位类型硕士
导师隋南
2000
学位授予单位中国科学院心理研究所
学位授予地点中国科学院心理研究所
学位专业基础心理学
关键词吗啡 成瘾 行为模型 脑组织损伤 皮质酮
摘要探讨药物行为效应的影响因素,建立稳定可靠的动物行为模型,是深入研究药物成瘾机制、探索有效干预手段的基本前提。应激或糖皮质激素水平以及学习记忆与药物成瘾的关系愈来愈受到人们的关注。本研究以条件性位置偏爱实验和局域内自发活动量测定方法,探讨了吗啡的强化和精神运动效应的影响因素,以组织学方法分析了不同剂量吗啡对大鼠脑组织的损伤以及应激刺激的影响,通过切除肾上腺考察了肾上腺皮质激素与吗啡精神运动效应的关系,并利用Morris水迷宫探索新的量化吗啡求药动机模型。结果表明小剂量吗啡条件性位置偏爱效应比较敏感,增加日训练次数可以缩短实验周期,但选择每次给药剂量时应避免连续给药之间的相互影响。慢性给予吗啡的自发活动量变化有明显的剂量、时间依赖性,此结果为慢性给药行为模型的参数选择了依据。小剂量吗啡的兴奋性精神运动效应之前也有短暂的抑制过程,纳络酮本身对自发活动量无明显影响但能拮抗吗啡的精神运动效应,该实验同时验证了通过减小剂量、缩短适应和观察时间而简化的局域内自发活动量测定方法的可靠性。吗啡的精神运动效应有赖于大鼠体内一定水平和功能的皮质酮的存在,提示个体皮质酮水平可能是决定成瘾易感性的重要因素。吗啡慢性作用下大鼠脑细胞变性程度与剂量有明显依赖关系,电击明显增强吗啡的损伤作用,提示应激还可能通过增强致瘾药物的神经损伤作用而增加成瘾易感性;皮层细胞损伤严重者可累及额叶、颞叶皮层及海马提示学习记忆机制可能与成瘾有密切关系。基于学习记忆模型,以Morris水迷宫建立新的量化求药动机的动物模型,取得初步的定性结果,吗啡可以延长小鼠找到站台的潜伏期而且纳络酮可以拮抗吗啡的这一作用。总之,本研究支持行为模型中剂量的选择应以小剂量为宜,为了更有效地对抗药物成瘾和复吸,应兼顾对应激等心理社会因素影响的控制和对可能存在的脑组织损伤的治疗,对新的量化求药动机模型的探索是值得进一步完善的有意义的尝试。
其他摘要Credible and stable animal behavioral models are necessary to research the mechanisms of addiction in vivo, especially to study the relationship between memory or stress and drug addiction, which has been one of the focuses in this field. So the object of this study was to observe the influences of several factors on the behavioral effects of morphine shown in the paradigms of conditioned place preference (CPP) and locomotor activity (LA), and to explore the effects of adrenalectomy on LA induced by morphine in rats. In addition, the cortexes of rats were examined, which were exposed to chronic administration of several doses of morphine with or without foot shock. Moreover, a new behavioral model was built to quantify the motivation of drug seeking. The results showed that CPP was more sensitive to low dose of morphine than to high dose. The period of experiment could be shortened by increasing the training times everyday, whereas in this way the dose of morphine should be low enough to avoid the impact between the near two exposures to morphine. Effects of chronic administration of morphine on LA in rats were dose- and time- dependent, which supplied evidence to choose parameters in other behavioral models. The results obtained by the simplified LA paradigm showed that hyperactivity of low dose of morphine following hypoactivity, and naloxone had no effects on LA but blocked the locomotion effects of morphine. Obvious effects of morphine on LA of rats might depend on a reasonable level of plasma corticosterone, which may determine individual vulnerability to drug addiction. Stress may also potentiate the vulnerability by aggravating damage to cortex of rats induced by drug dose-dependently, which is suggested by the results of histological examination. The result that frontal and temporal cortexes and hippocampus were injured suggests that there may be a close relationship between memory and drug addiction. It was showed that the new behavioral model on the basis of Morris water maze might be used to quantify the motivation of drug-craving.
页数73
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/4916
专题中国科学院心理研究所回溯数据库(1956-2010)
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陈晶. 影响吗啡动物行为效应的因素及其机制[D]. 中国科学院心理研究所. 中国科学院心理研究所,2000.
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