岛叶参与吗啡CPP的表达和树鼩慢性吗啡依赖模型的建立
文献类型：学位论文
| 作者 | 孙永梅 |
| 学位类别 | 硕士 |
| 答辩日期 | 2012-04 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 王建红 |
| 关键词 | 岛叶 吗啡 躯体感觉 树鼩 慢性依赖 |
| 其他题名 | Insular cortex is necessary for the expression of morphine conditioned place preference and the establishment of tree shrew chronic morphine dependent model |
| 学位专业 | 神经生物学 |
| 中文摘要 | 成瘾是一种慢性复发性脑疾病，给社会带来了巨大危害。与成瘾药物相伴的环境线索是导致复吸的因素之一。目前，关于环境线索是如何引起复吸的机制尚不清楚。在本研究中，我们建立了以触觉为主线索的大鼠吗啡条件性位置偏好（conditioned place preference, CPP），并且发现大鼠对伴吗啡箱的偏爱至少保持18天。继而，我们采用电解质损毁方法，探讨岛叶是否参与环境线索和吗啡奖赏的联合型学习和记忆。结果表明：在CPP条件化之前和CPP第一次测试后分别损毁具有躯体感觉功能的后岛叶，损伤了吗啡CPP的表达，但对CPP的获得却没有影响。以上结果提示后岛叶参与CPP的表达，其可能机制为：（1）后岛叶具有存储与躯体感觉相关的联合型记忆的功能；（2）后岛叶是渴求环路中的一个中转点。 吗啡是一种有效的镇痛药，但易使动物产生耐受性和成瘾性。在该实验中，中缅树鼩（Tupaia belangeri chinensis）经过连续五天，以每天三次肌肉注射吗啡（五天每次5、5、10、15、20 mg/kg，）后对吗啡产生耐受和依赖；吗啡注射4小时后，腹腔注射纳洛酮（1.25 mg/kg体重）催瘾，可诱导其产生条件性位置厌恶（Conditioned place aversion，CPA）及相应吗啡戒断症状。上述结果提示树鼩慢性吗啡依赖模型的建立，且该模型可用于研究吗啡依赖和耐受的生学机制，以及用于筛选能减轻戒断症状的药物。 |
| 英文摘要 | Addiction is a chronic brain disease which is characterized by relapse and it brings great damage to the society. Drug associated environment cues are one of the factors to prime relapse. However, the neurobiological mechanisms under how environment cues reinstate relapse are little known. In this study, we investigated whether the insular cortex participate in the formation and storage of associative memories between environmental cues and drug reward effects with electrolytic lesion and rat’s morphine conditioned place preference. Firstly, we established a rat morphine conditioned place preference paradigm with touch as the main environment cue and rats remained the preference to the morphine-conditioned compartments for at least 18 days. Then, we conducted the bilateral posterior insular lesion before the CPP training and one day after the first CPP test respectively. Our results showed that the posterior insula is necessary for the expression but not establishment of morphine CPP. The possible mechanisms of the posterior insula in the expression of CPP are: (1) this brain area has the function of storing associative memories related with somatosensory (2) the posterior insula is a relay in the craving circuit. The clinical use of morphine to reduce pain is limited for its tolerance, dependence and addiction. In the present study, the tree shrews（Tupaia belangeri chinensis）formed chronic morphine dependence through morphine-injections at increasing doses (5，5, 10, 15, 20mg/kg×3 times per day for 5 days). The naloxone (1.25 mg/kg)-induced conditioned place aversion (CPA) and the withdrawal symptom were found in the tree shrews. In addition, the tree shrews also showed morphine tolerance. Since the tree shrews are closer to the primates than the rodents in their evolutionary status and brain structure, the tree shrew model may be more advantageous than the rodent models in addictive research. The tree shrew model of chronic morphine dependence can be used to investigate the withdrawal symptoms in morphine dependence. This model is also a good candidate model for selecting potential drugs to reduce withdrawal symptoms caused by morphine. |
| 语种 | 中文 |
| 公开日期 | 2013-04-22 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7368]  |
| 专题 | 昆明动物研究所_神经系统编码 |
| 推荐引用方式 GB/T 7714 | 孙永梅. 岛叶参与吗啡CPP的表达和树鼩慢性吗啡依赖模型的建立[D]. 北京. 中国科学院研究生院. 2012. |
入库方式： OAI收割
来源：昆明动物研究所
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