| 题名 | ZIP干预岛叶对猕猴吗啡CPP及相关行为与生理指标的影响 |
| 作者 | 宗慰 |
| 学位类别 | 硕士 |
| 答辩日期 | 2013-05 |
| 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 | PKMzeta ZIP 猕猴 岛叶 吗啡 条件性位置偏好 |
| 其他题名 | ZIP injection to insular cortex interfere CPP scores and related behavioral physiological indexes on morphine treated macaques |
| 学位专业 | 神经生物学 |
| 中文摘要 | 岛叶与众多脑区互有投射，是内脏运动和感觉的高级整合皮层。岛叶可能参与整合储存成瘾药物带给躯体及内脏的愉悦感，因而与药物依赖的线索记忆有关。这种线索记忆的形成，可能部分或全部依赖于蛋白激酶Mzeta（PKMzeta）介导和维持的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体向突触后膜迁移并上膜而形成的长时程增强（LTP）；而PKMzeta的假底物zeta抑制肽（ZIP）则可以使上膜的AMPA受体被内吞下膜，从而反转PKMzeta介导维持的LTP，因而可以消减甚至抹除靠这一机制编码的记忆信息。猕猴是常用的非人灵长类实验动物，其在种系发生上相比啮齿类与人类的相似性更高，尤其前额叶发育程度和认知能力更是啮齿类无法比拟的。我们利用吗啡诱导在猕猴建立了条件性位置偏好（CPP）模型，通过测试猕猴对吗啡匹配房的偏好程度来评估成瘾药物相关记忆是否存在及再现水平。通过向建立了吗啡相关记忆的猕猴的岛叶注射ZIP，发现ZIP显著降低CPP的表达程度。由于PKMzeta参与了岛叶编码的条件性味觉厌恶（CTA）记忆；岛叶和前额叶存在投射；焦虑和寻药及成瘾存在关联；岛叶和嗅觉、味觉的整合有关，因而，我们同时观察ZIP干预岛叶对CTA记忆的影响，肌注吗啡和岛叶给ZIP对工作记忆、血浆皮质醇水平以及饮食行为的影响，发现血浆皮质醇水平在手术后降低，在吗啡后应激模式改变。 |
| 英文摘要 | The insular cortex is intergration cortex of viscerosensory and visceromotor, which has projections with many encephalic regions. Insular lobe may has relation with cue memory of drug dependence due to its function of integrating and storing delighted memory from soma and viscera stimulated by drug use.The mechanism of this cue memory may completely or partly depend on function of PKMzeta, which induces and maintains LTP by increasing the number of AMPA receptor in post synapse.While PKMzeta pseudosubstrate zeta inhibitory peptide(ZIP) can reverse PKMzeta mediated LTP thus disrupt or even erase the memory depending on PKMzeta through endocytosis of AMPA receptors which decreasing the receptor’s number in post synapse. Rhesus macaques are commonly used nonhuman primate experimental animals which have more phylogenic similarity with Homo sapien than rodents especially in advanced prefrontal lobe development and cognitive ability. Morphine induced conditioned place preference(CPP) model can be established in rhesus macaques. The drug associated memory can be assessed by this preference model. We injected ZIP to insular lobe on morphine induced CPP macaques, and reduced the preference significantly. PKMzeta in insular lobe was reported to associate with conditioned taste aversion(CTA) memomry, we observed none significant result of ZIP injection to insular in macaques. Working memory (there are projections between insular and prefrontal lobe), plasma cortisone level(the relationship between anxiety and addiction) and cibation behavior (insular lobe integrates olfactory and gustatory messages) were also observed. We found plasma cortisone level decrease after surgery and the response mode to stress changed after morphine. |
| 语种 | 中文 |
| 公开日期 | 2013-06-17 |
| 内容类型 | 学位论文 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7482]  |
| 专题 | 昆明动物研究所_神经系统编码 |
| 推荐引用方式 GB/T 7714 | 宗慰. ZIP干预岛叶对猕猴吗啡CPP及相关行为与生理指标的影响[D]. 北京. 中国科学院研究生院. 2013. |
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