| 题名 | 慢性阿片类物质滥用对空间认知功能的影响及嗅觉系统与吗啡成瘾的相互作用 |
| 作者 | 刘小粉 |
| 学位类别 | 博士 |
| 答辩日期 | 2009-06 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 马原野 |
| 关键词 | 吗啡 海洛因 成瘾 海马 空间认知 单细胞放电 Y-迷宫 气味 线索渴求 CPP 嗅觉功能 嗅觉阈值 嗅觉辨别 嗅觉记忆 |
| 其他题名 | The effects of chronic opioid abuse in spatial congnitive function and the interaction between olfactory system and morphine addiction. |
| 中文摘要 | Ⅰ 慢性阿片类物质滥用对空间认知功能的影响 本章首先对成瘾的神经生物学机制进行综述，然后介绍我的实验研究内容，实验目的是探讨海马在阿片类成瘾中的作用，及阿片类物质滥用对空间认知功能的影响。 实验1采用单细胞记录技术，记录自由活动大鼠在慢性吗啡给予后戒断期间海马CA1区神经元发放频率，比较其在吗啡相关环境（阳性环境）及无关环境（阴性环境）中神经元发放频率的变化，且比较神经元发放变化率在各组间的差异。实验2检测了在海洛因戒断初期海洛因依赖者的地图/图标跟随及地图/图标工作记忆的能力。实验3采用Y迷宫行为范式检测在戒断不同时期，慢性吗啡给予对小鼠Y迷宫空间识别能力的影响。实验结果如下： 实验1：吗啡戒断后，大鼠海马CA1区部分神经元在阳性环境及阴性环境中的发放率有显著性差异，这些神经元分为两类：Ⅰ类神经元在阳性环境中发放频率高于在阴性环境，Ⅱ类神经元在阳性环境中发放频率低于在阴性环境，其中吗啡组的Ⅱ类神经元发放变化率与盐水组相比存在显著性差异。 实验2：海洛因依赖者，尤其女性海洛因依赖者，在地图跟随及地图/图标工作记忆中的成绩明显低于正常被试。 实验3：在吗啡戒断第2天、第9天、第19天，小鼠Y迷宫空间识别记忆能力均受到损伤。 以上实验结果表明，海马神经元在吗啡相关环境与无关环境中发放频率不同，从而编码了环境刺激与药物经历相关的记忆，在阿片类药物成瘾中起到一定作用；以及阿片类物质滥用损伤了大脑空间认知功能。 Ⅱ 嗅觉系统与吗啡成瘾的相互作用 本章首先对嗅觉系统的功能及脑疾病引起嗅觉功能异常进行了综述，然后介绍我的实验研究内容，实验目的是探讨嗅觉系统在吗啡成瘾过程中的作用，及慢性吗啡给予对嗅觉功能的影响。 实验1：利用条件化位置偏好模型（CPP），研究气味线索对吗啡依赖及渴求的影响。结果发现，单一嗅觉刺激使小鼠建立条件化位置偏好，形成吗啡依赖。当改变外界环境，动物进入完全新异的环境，依然寻求与吗啡相关的气味线索，说明吗啡相关气味线索能有效诱发小鼠对吗啡的渴求。 实验2：研究短期及长期吗啡给予后小鼠嗅觉功能的变化。结果发现， 4天或21天的吗啡给予导致小鼠嗅觉敏感度降低（嗅觉阈值升高），而嗅觉辨别能力没有显著影响。小鼠嗅觉记忆能力受到损伤，随着吗啡给予时间的延长，这种记忆损伤更加明显。 我们的实验表明嗅觉系统在吗啡依赖及渴求过程起到非常重要的作用，吗啡成瘾导致部分嗅觉功能的损伤。与药物相关的环境线索是诱发渴求及复吸的原因之一，因此，至少在啮齿类动物模型上，用嗅觉刺激作为药物相关的环境线索来研究渴求及复吸的机制，可能是较好的研究方法。 |
| 英文摘要 | Ⅰ The effects of chronic opioid abuse in spatial recognition function The chapter firstly reviewed neural mechanisms of addiction and reported three experiments during my postgraduate period. The purposes of the experiments were to demonstrate the function of hippocampal CA1 in drug addiction and the effects of chronic opioid abuse in spatial congnitive function. In experiment 1, with single-unit recording technique in freely-moving rats, spontaneous activities in the hippocampal CA1 region neurons during the morphine withdrawal period were recorded, which were compared in drug paired environment (positive environment) and unpaired environment(negative environment).We also compaired the spike frequency between morphine-treated group and saline-treated group. In experiment 2, Male and female heroin-dependent patients (HDPs) matched with “normal” people were tested on 4 topographical orientation tasks: schematic map-following, map-memory, schematic picture-following, and picture-memory tasks. In experiment 3, spatial recognition memory was tested in the Y-maze on the 2nd, 9th and 19th withdrawal day. Our results are as follows: Expeiment 1: During the morphine withdrawal period ,some of the neurons in the hippocampus CA1 region have the different spike frequencies between the positive and negative environments,which could be separated into two types: typeⅠis the ones which have the higher spike frequencies in the positive environment than in the negative ; typeⅡ is the ones which have the lower in the positive environment than in the negative. And the spike frequencies of the type Ⅱ neurons are significantly different between the two groups. Experiment 2: HDPs, especially, female HDPs demonstrat greater performance deficits in map-following and map-picture-memory tasks than did in normal controls. Experiment 3: spatial recognition memory of morphine-treated mice is impaired on each of the three test days. Our study clearly suggests that long-term morphine use leads to more persistent impairments of spatial recognition memory. These results demonstrated that the altered spike frequency of hippocampal neurons in the positive and negative environments may play a role in encoding process of drug-specific contextual memory formation. Chronic drug abuse caused dysfunction in congnitve spatial function. Ⅱ The interaction between olfactory system and morphine addiction We reviewed the olfactory function and dysfunction in brain disease firstly in the chapter, and then, reported two experiments during my postgraduate period. The purpose of the part was to demonstrate the function of olfactory system in morphine addiction, in contrast, the effects of chronic morphine administration in olfactory system. Experiment 1: In the study, we investigated the dependence and psychological craving of morphine in mice using the conditioned place preference (CPP) paradigm, and the only odor cue as conditioned stimulus (CS).The results showed that pairing morphine with an odor in mice produced a conditioned preference. When the mice were exposed to a totally different environment during morphine withdrawal, they spent significant more time in the chambers with morphine-paired odor. The studies indicate that an odor may serve as an effective stimulus to initiate morphine craving in mice. Experiment 2: In the study, on d 5 and d 22 which mice withdrew from morphine for at least 24 hours after 4-day or 21-day morphine injection, the olfactory function of mice was tested. The morphine-treated mice showed significantly impaired olfactory sensitivity (raised threshold) and olfactory memory, but normal olfactory discrimination compared with the saline controls either on d 5 or d 22. The findings indicate that long-lasting morphine use causes more severe odor memory impairments. The studies demonstrate that the importance of olfactory system in morphine addiction and chronic morphine abuse impaired the olfactory function in mice. Cues associated with previous drug use can initiate drug craving and relapse in addicts. Therefore, to test the mechanisms of cue-induced craving and relapse using an odor previously paired with drugs as a conditioned cue, may be a good method, at least in rodents. |
| 语种 | 中文 |
| 公开日期 | 2010-10-22 |
| 内容类型 | 学位论文 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6302]  |
| 专题 | 昆明动物研究所_认知障碍病理学 |
| 推荐引用方式 GB/T 7714 | 刘小粉. 慢性阿片类物质滥用对空间认知功能的影响及嗅觉系统与吗啡成瘾的相互作用[D]. 北京. 中国科学院研究生院. 2009. |
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