PHARMACOLOGY OF COGNITIVE MEMORY IN MONKEYS

猴子认知记忆的药理学

• 批准号: 5203697
• 负责人: T G AIGNER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203697
• 关键词: Macaca; NMDA receptors; acetylcholine; behavioral habituation /sensitization; cognition; dentate gyrus; experimental brain lesion; habits; hippocampus; memory; physostigmine; prosencephalon; psychological tests; psychopharmacology; scopolamine; self medication

Patients with Alzheimer's disease have, among other abnormalities, loss of markers for acetylcholine and glutamate. The impaired memory accompanying this disease suggests a critical function for these two neurochemicals in mnemonic processes. In support of this proposal, we have found that visual recognition memory in macaques is impaired following either excitotoxic lesions of the basal forebrain cholinergic system or administration in normal monkeys of the muscarinic receptor antagonist scopolamine and the NMDA-type glutamate receptor antagonist MK-801. In addition, we found that scopolamine affects primary as well as secondary memory, and memory storage, not retrieval. We have shown that the cholinesterase inhibitors physostigmine, THA, and E2020 all produce significant, though small, improvements in performance. Additionally, we have found that D-cycloserine, an agonist at the glycine binding site on the NMDA receptor, produces an even greater improvement in memory than do the cholinesterase inhibitors. Using in vivo microdialysis, we have shown that acetylcholine release is increased in the hippocampus and inferior temporal and perirhinal cortices when an animal is actively performing any task compared to when it is sitting quietly. Using direct intracranial injections, we have found that scopolamine impairs recognition when injected into the perirhinal cortex, but not into the inferior temporal cortex or the dentate gyrus of the hippocampus.

阿尔茨海默氏病患者除了其他异常之外，还会丧失 乙酰胆碱和谷氨酸标记物。 记忆力受损 伴随这种疾病表明这两个功能具有关键功能 记忆过程中的神经化学物质。 为了支持这项提议，我们 发现猕猴的视觉识别记忆受损 基底前脑胆碱能兴奋性毒性损伤后 毒蕈碱受体的系统或在正常猴中的施用 拮抗剂东莨菪碱和 NMDA 型谷氨酸受体拮抗剂 MK-801。 此外，我们发现东莨菪碱也影响原发性 作为辅助记忆，是记忆存储，而不是检索。 我们已经展示了 胆碱酯酶抑制剂毒扁豆碱、THA 和 E2020 均 对性能产生显着（尽管很小）的改进。 此外，我们还发现 D-环丝氨酸，一种甘氨酸激动剂 NMDA 受体上的结合位点，产生更大的改善 记忆力优于胆碱酯酶抑制剂。 体内使用 微透析，我们发现乙酰胆碱释放增加 当海马体、颞下皮质和鼻周皮质 与坐着时相比，动物正在积极地执行任何任务 悄悄。 通过直接颅内注射，我们发现 东莨菪碱注射到鼻周皮层时会损害识别能力， 但不进入颞下皮层或齿状回 海马体。