BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

在过去的十年里，已经发现了四十多种多肽 定位于哺乳动物大脑的神经元。多肽共存的多个病例 与经典神经递质相同的神经元中的神经递质已被描述。我们的 实验室正在研究共存的功能意义 中枢神经系统中的多肽和递质，使用行为 工具。 A)我们之前已经证明，CCK可以增强 多巴胺引起伏隔核超运动，CCK和 多巴胺共存。今年，我们开始研究功能性的 内源性CCK的意义。我们开发了一种方法 刺激腹侧被盖，以某种方式增加运动行为 类似于伏核内微量注射多巴胺。初步 数据显示，CCK拮抗剂丙谷胺可阻断多动症 由VTA刺激诱导，为VTA的功能作用提供证据 中脑边缘通路中的内源性CCK。 B)P物质(SP)、促肾上腺皮质激素释放因子(CRF) 乙酰胆碱酯酶(Ach E)在背外侧区共存 投射到大鼠前额叶皮质的被盖神经元。P物质 增强，而CRF抑制，卡巴胆碱诱导的“拳击”。今年我们 发现P物质拮抗剂可以阻断卡巴胆碱诱导的“拳击”， 为内源性P物质在心力衰竭中的功能作用提供证据 内侧前额叶皮质。 C)催产素和缩胆囊素共存于视上核和视网膜区。 下丘脑室旁核。突触后插管 这种共存的地点和对梳理行为的评估揭示了 微量注射CCK与Oxy的竞争性相互作用。第三个案例 共存的，即两个没有初级递质的肽，似乎 具有与A和A中概述的案例不同的交互机制 胡麻B.

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, where CCK and dopamine coexist. This year, we began to investigate the functional significance of endogenous CCK. We developed a method to electrically stimulate the ventral tegmentum to increase locomotor behavior in a manner analogous to microinjection of DA into the nucleus accumbens. Preliminary data suggest that the CCK antagonist, proglumide, blocks hyperlocomotion induced by VTA stimulation, providing evidence for a functional role of endogenous CCK in the mesolimbic pathway. B) Substance P (SP), corticotropin releasing factor (CRF) and acetylcholinesterase (Ach E) were found to coexist in dorsolateral tegmental neurons projecting to the rat prefrontal cortex. Substance P potentiated, while CRF inhibited, carbachol-induced "boxing". This year we found that substance P antagonists block carbachol-induced "boxing," providing evidence for a functional role of endogenous substance P in the medial prefrontal cortex. C) Oxytocin and cholecystokinin coexist in the supraoptic and paraventricular nuclei of the hypothalamus. Cannulation of postsynaptic sites of this coexistence and evaluation of grooming behavior revealed a competitive interaction between microinjected CCK and OXY. This third case of coexistence, i.e., two peptides with no primary transmitter, appears to have a different mechanism of interaction from the cases outlined in A and B.