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题名阿片和多巴胺,胆碱,谷氨酸神经递质在学习记忆中的作用
作者王建红
学位类别博士
答辩日期2007-06
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 多巴胺 乙酰胆碱 NMDA 学习记忆
其他题名Effects of opiate and dopaminergic, cholinergic, glutamatergic neurotransmitters on learning and memory
学位专业神经生物学
中文摘要阿片,多巴胺、胆碱及谷氨酸神经递质系统在学习记忆中起着重要作用,且它们之间存在着相互关系,它们的功能失调和人类一些精神疾病密切相关。本论文分别探讨了这4类递质系统在学习记忆中的作用,并选用不同剂量的吗啡合并多巴胺受体激动剂和拮抗剂,胆碱拮抗剂,NMDA受体拮抗剂在小鼠和猕猴空间记忆任务中,检测阿片和这些神经递质系统之间的相互关系。结果发现:吗啡依赖于剂量和任务间隔地致使小鼠Y-迷宫空间识别记忆和猕猴工作记忆受损;海洛因依赖患者出现依赖性别和任务方向的地图/图标跟随和记忆认知障碍;多巴胺受体激动剂和拮抗剂对小鼠和猕猴的空间记忆有不同影响;胚胎期及成长期阻断多巴胺受体功能,可引起小鼠一系列学习记忆及活动性改变,撤药后是否逆转根据不同的抗精神病药物而不同;乙酰胆碱受体拮抗剂损伤小鼠和猕猴的空间记忆;NMDA受体拮抗剂氯胺酮可使小鼠空间记忆巩固过程受损,但不影响非空间记忆;MK-801损伤猕猴迷宫空间记忆再现,并降低2种延缓反应的工作记忆;当合并吗啡和其它神经递质药物时,可见吗啡和多巴胺受体激动剂和拮抗剂,乙酰胆碱受体拮抗剂,NMDA受体拮抗剂均有不同程度的相互作用,有关作用机制还有待进一步实验的探讨。了解阿片和其它神经递质系统相互作用的机制将有助于揭示药物成瘾的生化机理,寻找药物心理成瘾等神经精神疾病的治疗手段和策略。
英文摘要Opiate, dopaminergic, cholinergic and glutamatergic neurotransmitters play key roles in learning and memory. Interactions were found between these neurotransmitters and dysfunction of them may induce human diseases including mental disorders. In the present studies, the effects of these neurotransmitters on cognition were confirmed, and the interactions of these systems were evaluated by co-administrations of morphine and dopamine (DA) agonists/antagonists, acetylcholine (ACh) antagonists, NMDA antagonist in mice and monkeys using Y-maze and WGTA tasks. The results showed that: Morphine impaired mice spatial recognition memory and monkeys working memory with dose dependence. Heroin impaired map/picture following and memory tasks dependent on gender and orientation of the tasks. DA agonists/antagonists had different effects on memory in mice and monkeys. Effects of prenatal and postnatal chronic clozapine/haloperidol on memory and activity in mouse offspring were differently lasting. ACh antagonists (scopolamine/atropine) caused impairment of memory in mice and monkeys. NMDA blocker, ketamine affected memory consolidation in a differential manner in mice T-maze and passive avoidance paradigms. Another NMDA antagonist, MK-801 impaired maze spatial memory and working memory in monkeys. Morphine-dopamine, morphine- acetylcholine, morphine-NMDA interactions in memory were found in mice Y-maze and monkeys WGTA tasks. Understanding the interaction of opiate and other neurotransmitters may gain insight into human addiction and mental disorders.
语种中文
公开日期2010-10-15
内容类型学位论文
源URL[http://159.226.149.42:8088/handle/152453/6274]  
专题昆明动物研究所_认知障碍病理学
昆明动物研究所_神经系统编码
推荐引用方式
GB/T 7714
王建红. 阿片和多巴胺,胆碱,谷氨酸神经递质在学习记忆中的作用[D]. 北京. 中国科学院研究生院. 2007.
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