CCK AND MIDBRAIN DA SYSTEMS: SPECIFICITY OF ACTIONS

脑内含多巴胺(DA)神经元的亚群 中脑的A9和A10区域含有这种多肽 胆囊激肽(CCK)。静脉注射和微离子导入 应用CCK有效地兴奋DA细胞的一个亚群 这可能与那些也含有CCK的细胞相对应。在……里面 除了这种短暂的兴奋，CCK还施加了更持久的 多巴胺神经元对其敏感性的调制效应 静脉注射阿朴吗啡和阿朴吗啡的抑制作用 微离子导入DA。初步研究表明， CCK的兴奋和调制作用也可以发生。 独立地和发源于 静脉注射CCK似乎对中脑有不同的影响。 鉴于中脑DA系统与我们目前的 关于几种神经学和神经生物学的假说 精神障碍，一系列研究建议开始 更详细地探索CCK与已确定的DA的相互作用 神经元亚群。总体而言，该领域的进展 CCK研究因缺乏具体和 强大的敌手。几种新的CCK拮抗剂 中枢和/或外周CCK受体的亲和力 发展起来的。在目前的提案中，这些化合物将是 用来研究受体的特异性 CCK对已鉴定亚群的电生理效应 多巴胺神经元。此外，直接性和调制性 CCK对纹状体神经元的电生理作用 表征并比较了刺激的效果 纹状体CCK传入。希望所获得的信息 这些研究将使我们更好地理解 不同的中脑DA神经元通路的生理学。这 知识，结合解剖学和 生化技术，可能有助于制定可检测的 中枢神经系统疾病的病因学假说 DA神经元功能障碍。

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.