DOPAMINE-NEUROPEPTIDE COEXISTENCE AND MENTAL FUNCTION

本项目为神经科学工作组在心理健康 将在纽约大学医学中心进行， 卡罗林斯卡学院，斯德哥尔摩，并将调查的作用， 多巴胺能和肽能神经元系统在中枢神经系统功能中的作用 生理和病理状态。 解剖学上的，生物化学上的 多巴胺（DA）神经元的生理异质性将 被研究。 免疫组织化学，结合原位 杂交和逆行追踪，将用于研究 DA的定位和细胞分化以及特异性 神经肽以及非递质蛋白质。 这三 程序是一种补充方法， 比任何一个单独的组合都强大。 的共定位 DA与其他递质和非递质物质将 识别DA神经元的不同子集，并可作为标记物 对于特定的DA神经元子集，它们共享某些调节功能， 机制等 将有可能定量地建立 酪氨酸羟化酶（TH）mRNA在不同DA 人群，并定义TH在不同人群中的表达率。 中脑DA细胞与共存肽的关系。 的 对急性和慢性精神抑制剂的反应性差异 治疗可归因于自身受体的密度 调节不同前脑DA的合成和/或释放 DA神经支配 因此，可以定义不同的 中脑DA神经元群体的基础上， D2 DA受体结合位点的免疫组织化学染色。 此外，涉及脱敏的机制， 将研究各种DA受体亚型， D1 DA受体结合蛋白与腺苷酸环化酶之间的关系 非精神分裂症患者和精神分裂症患者的死后大脑 研究了

This program project for Neuroscience Work Groups in Mental Health will be carried out at New York University Medical Center and Karolinska Institute, Stockholm, and will investigate the role of dopaminergic and peptidergic neuronal systems in CNS function in physiological and pathological states. The anatomical, biochemical and physiological heterogeneities of the dopamine (DA) neurons will be studied. Immunohistochemistry, in combination with in situ hybridization and retrograde tracing, will be used for studies on localization and cellular differentiation of DA and specific neuropeptides, as well nontransmitter proteins. These three procedures represent complementary methodology and are much more powerful in combination than any one alone. The colocalization of DA with other transmitter and nontransmitter substances will identify distinct subsets of DA neurons, and may serve as a marker for specific subsets of DA neurons which share certain regulatory mechanisms. It will be possible to quantitatively establish differences in tyrosine hydroxylase (TH) mRNA in different DA populations and define the rate of expression of TH in different midbrain DA cells in relation to coexistent peptides. The differences in responsiveness to acute and chronic neuroleptic treatment may be attributable to the density of autoreceptors regulating synthesis and/or release of DA in different forebrain DA innervation. It may therefore be possible to define distinct populations of midbrain DA neurons on the basis of immunohistochemical staining for the D2 DA receptor binding sites. Furthermore, the mechanisms involved in the desensitization of various DA receptor subtypes will be investigated and the coupling between D1 DA receptor binding protein and adenylate cyclase in postmortem non-schizophrenic and schizophrenic brain will be studied.