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.

阿尔茨海默氏病的患者除其他异常外，还丧失 乙酰胆碱和谷氨酸的标记物。 记忆力受损 伴随这种疾病表明这两个的关键功能 助记符过程中的神经化学物质。 为了支持该提议，我们 发现猕猴中的视觉识别记忆受损 遵循基础前脑胆碱能的兴奋性病变 毒蕈碱受体正常猴子的系统或给药 拮抗剂东pol碱和NMDA型谷氨酸受体拮抗剂 MK-801。 此外，我们发现东pol碱也会影响主要 作为次要内存和内存存储，而不是检索。 我们已经显示了 胆碱酯酶抑制剂Physostigmine，tha和e2020 ast 产生显着的性能改善。 此外，我们发现D-Cycloserine是甘氨酸的激动剂 NMDA受体上的结合位点会产生更大的改进 在记忆中，胆碱酯酶抑制剂比胆碱酯酶抑制剂。 使用体内 微透析，我们已经表明乙酰胆碱释放在 当海马和下颞和周围皮质时 与坐着相比，动物正在积极执行任何任务 悄悄。 使用直接颅内注射，我们发现 注射到周围皮层时会损害识别 但不进入下颞皮质或齿状回 海马。