BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

在过去的十年中，已经发现了40种或更多的肽 存在于哺乳动物大脑的神经元中。 许多情况下，肽共存 在同一个神经元与经典的递质已被描述。 我们 实验室正在研究共存的功能意义， 中枢神经系统中的肽和递质，使用行为 工具. A）我们以前表明，胆囊收缩素（CCK）增强 多巴胺诱导的丘脑核运动过度，其中CCK和 多巴胺共存。 今年，我们开始研究功能性 内源性CCK的意义 我们发明了一种方法 刺激腹侧被盖以增加运动行为， 类似于将DA显微注射到延髓核中。 初步 数据表明，CCK拮抗剂丙谷胺可阻断过度运动， 通过VTA刺激诱导，提供了功能作用的证据， 内源性CCK的mesolimbic途径。 B）P物质（SP）、促肾上腺皮质激素释放因子（CRF）和 乙酰胆碱酯酶（Ach E）在背外侧 投射到大鼠前额皮质的被盖神经元。 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物质拮抗剂阻断卡巴胆碱诱导的“拳击”， 提供了内源性P物质在细胞内的功能作用的证据。 内侧前额叶皮层 C）催产素和胆囊收缩素共存于视上区和视下区。 下丘脑室旁核。 突触后套管 这种共存的网站和梳理行为的评价揭示了一个 CCK和OXY之间的竞争性相互作用。 这第三个案子 共存，即，两种没有初级递质的肽， 与A中概述的情况有不同的相互作用机制， 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.