CCK AND MIDBRAIN DA SYSTEMS: SPECIFICITY OF ACTIONS

CCK 和中脑 DA 系统：行动的特异性

• 批准号: 3381211
• 负责人: ARTHUR S FREEMAN
• 金额: $ 6.09万
• 依托单位: SINAI HOSPITAL OF DETROIT
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381211
• 关键词: afferent nerve; albino rat; apomorphine; brain cell; brain electrical activity; brain mapping; caudate nucleus; cell population study; cholecystokinin; computer data analysis; dopamine; dopamine receptor; drug administration routes; drug interactions; electrophysiology; electrostimulus; hormone receptor; injection /infusion; mesencephalon; neural transmission; neurotransmitters; nontherapeutic iontophoresis; receptor sensitivity; substantia nigra

Subpopulations of dopamine (DA)-containing neurons within the A9 and A10 regions of the midbrain contain the peptide cholecysto-kinin (CCK). Intravenously and microiontophoretically administered CCK potently excites a subpopulation of DA cells that may correspond to those cells which also contain CCK. In addition to this transient excitation, CCK exerts a more enduring modulatory effect on DA neurons with regard to their sensitivity to the inhibitory effects of intravenous apomorphine and microiontophoretic DA. Preliminary studies have shown that the excitatory and modulatory effects of CCK can also occur independently and that distinct DA pathways originating in the midbrain appear to be differentially affected by intravenous CCK. Given the relevance of midbrain DA systems to our current hypotheses regarding the neurobiology of several neurological and psychiatric disorders, a series of studies are proposed to begin to explore in more detail the interactions of CCK with identified DA neuronal subpopulations. In general, advancements in the field of CCK research have been hindered by the lack of specific and potent antagonists. Several new CCK antagonists with high affinity for central and/or peripheral CCK receptors have been developed. In the present proposal, these compounds will be employed to investigate the receptor specificity of the electrophysiological effects of CCK on identified subpopulations of DA neurons. In addition, the direct and modulatory electrophysiological effects of CCK on striatal neurons will be characterized and compared to the effects of stimulation of striatal CCK afferents. It is hoped that the information obtained from these studies will lead to a better understanding of the physiology of distinct midbrain DA neuronal pathways. This knowledge, combined with that obtained with anatomical and biochemical techniques, may aid in the formulation of testable hypotheses concerning the etiology of disorders linked to central DA neuronal dysfunction.

多巴胺（DA）的亚群 - 含有神经元的神经元 中脑的A9和A10区域包含肽 胆囊基因蛋白（CCK）。 静脉内和微胎面 管理的CCK有效激发了DA细胞的亚群 这可能对应于那些也包含CCK的单元。 在 除了这种瞬态激发，CCK施加了更持久的 对DA神经元的敏感性的调节作用 静脉注射载吗啡的抑制作用和 微摄取的DA。 初步研究表明 CCK的兴奋性和调节作用也可能发生 独立和那种起源于 中脑似乎受静脉内CCK的差异影响。 鉴于中脑DA系统与我们当前的相关性 关于几种神经系统神经生物学的假设 精神疾病，提出了一系列研究以开始 更详细地探索CCK与已识别DA的相互作用 神经元亚群。 一般而言，领域的进步 CCK研究受到缺乏具体和 有效的对手。 几个新的CCK拮抗剂高 对中央和/或外围CCK受体的亲和力已经 发达。 在目前的建议中，这些化合物将是 用于调查受体特异性 CCK对已识别亚群的电生理影响 da神经元。 另外，直接和调节 CCK对纹状体神经元的电生理影响将是 表征并将其与刺激的影响 纹状体CCK传入。 希望获得的信息 从这些研究将使人们更好地理解 独特的中脑DA神经元途径的生理学。 这 知识，与解剖学和 生化技术可能有助于制定可测试的 关于与中央有关的疾病的病因的假设 DA神经元功能障碍。