BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

神经肽的行为功能

• 批准号: 3944707
• 负责人: J N CRAWLEY
• 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/3944707
• 关键词: Alzheimer's disease; acetylcholine; adrenergic agents; anticholinergic agent; atropine; brain mapping; brain metabolism; cerebral ventricles; cholecystokinin; chordate locomotion; disease /disorder model; dopamine; drug interactions; limbic system; mecamylamine; microinjections; neural information processing; neurons; neuropharmacology; neurotransmitters; nucleus accumbens; somatostatin; substantia innominata; tegmentum

The past decade has witnessed the discovery of forty or more peptides localized in neurons of mammalian brain. Many cases of peptides coexisting in the same neuron with classical transmitters have been described. Our laboratory is investigating the functional significance of coexisting peptides and transmitters in the central nervous system, using behavioral tools. A) We previously showed that cholecystokinin (CCK) potentiates dopamine-induced hyperlocomotion in the nucleus accumbens, the terminal region of the mesolimbic pathway where CCK and DA coexist. This year, we began to characterize the role of CCK on DA autoreceptors in the ventral tegmentum (VTA), the cell body region of the mesolimbic pathway where CK an DA coexist. Preliminary data show that CCK potentiates the hypolocomotion induced by DA in the VTA, while having no effect alone, i.e. the potentiating effect of CCK in the VTA was not blocked by doses of proglumide which blocked the potentiating effect of CCK in the nucleus accumbens. In addition, the unsulfated form of CCK- 8 was also active in potentiating DA-induced hypolocomotion in the VTA. These preliminary behavioral data suggest that the pharmacology of CCK effects in the VTA match the "central- type" CCK-receptor, as found by Skirboll and Hommer using electrophysiological techniques. Conversely, the pharmacology of CCK effects in the nucleus accumbens match the "peripheral- type" CCK receptor in our previous behavioral data. B) The nucleus basalis of Meynert lesion rat model of Alzeheimer's disease is now ongoing in our laboratory. We have completed one experiment showing that acetylcholine (ACH) can reverse the memory deficit in a T-maze task when given directly into the lateral ventricles, the first demonstration of a central site of action for ACH. The second experiment found that atropine, but not mecamylamine, blocked the ACH effect, suggesting the involvement of a muscarinic, rather than a nicotinic cholinergic receptor. Tests of somatostatin and galanin, alone and in combination with a submaximal dose of ACH, are in progress.

过去十年见证了四十个或更多的发现 肽位于哺乳动物大脑的神经元中。 很多案例 肽与经典递质共存于同一神经元中 已被描述。 我们的实验室正在研究 共存肽和递质的功能意义 中枢神经系统，使用行为工具。 A) 我们之前表明胆囊收缩素 (CCK) 可以增强 多巴胺引起的伏隔核过度运动 中脑边缘通路的末端区域，其中 CCK 和 DA 共存。 今年，我们开始描述 CCK 在 腹侧被盖 (VTA)（细胞体）中的 DA 自身受体 中脑边缘通路区域，CK 和 DA 共存。 初步数据显示 CCK 增强运动功能减退 由 VTA 中的 DA 诱导，但单独没有作用，即 CCK 在 VTA 中的增强作用不会被剂量所阻断 丙谷胺可阻断 CCK 的增强作用 伏隔核。 此外，CCK-的非硫酸化形式 8 也能有效增强 DA 诱导的运动不足 VTA。 这些初步的行为数据表明 CCK 在 VTA 中的药理学作用与“中枢- 型”CCK 受体，由 Skirboll 和 Hommer 使用发现 电生理学技术。 相反，药理学 伏隔核中的 CCK 效应与“外周- 类型”CCK受体在我们之前的行为数据中。 B) Meynert 损伤大鼠模型的基底核 阿尔茨海默氏病目前正在我们的实验室进行研究。 我们有 完成了一项实验，表明乙酰胆碱 (ACH) 可以 直接给予 T 迷宫任务时可逆转记忆缺陷 进入侧脑室，中枢神经系统的第一个演示 ACH 的作用地点。 第二个实验发现 阿托品，但不是美加明，阻断了 ACH 效应， 表明毒蕈碱的参与，而不是 烟碱胆碱能受体。 生长抑素和甘丙肽的测试， 单独使用或与次最大剂量的 ACH 联合使用，均有效 进步。