BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

在过去的十年里，已经发现了四十个或更多 多肽定位于哺乳动物大脑的神经元中。许多情况下 与经典递质共存于同一神经元的多肽 都被描述过。我们的实验室正在调查 体内共存多肽和递质的功能意义 中枢神经系统，使用行为工具。 A)我们之前已经证明，CCK可以增强 多巴胺引起的伏隔核超运动， CCK和DA所在的中脑边缘通路的终端区 共存。今年，我们开始将CCK的角色定性为 腹侧被盖(VTA)细胞体中的DA自身受体 中脑边缘通路中CK和DA共存的区域。 初步数据显示，CCK可增强低血压 在VTA中由DA诱导，而不单独起作用，即 CCK对VTA的增强作用不受剂量的影响 丙谷胺阻断CCK的增强作用 伏隔核。此外，CCK的非硫酸形式- 8还能增强DA引起的大鼠心肌细胞收缩反应 VTA。这些初步的行为数据表明， CCK在VTA中的药理作用与“中枢- Skirboll和Hommer使用 电生理技术。相反，它的药理作用 伏隔核中的CCK效应与“外周- 在我们之前的行为数据中输入“CCK受体。 B)Meynert损毁大鼠模型的基底核 阿尔泽海默氏症现在正在我们的实验室进行。我们有 完成了一项实验，表明乙酰胆碱(ACH)可以 在T型迷宫任务中直接给予时逆转记忆缺陷 进入侧脑室，第一次展示了一种 ACH的行动地点。第二个实验发现， 阿托品，而不是甲乙胺，阻断了ACH效应， 暗示了毒枭的参与，而不是 烟碱胆碱能受体。生长抑素和甘丙素的检测， 单独和与亚最大剂量的ACH联合使用 进步。

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.