CHARACTERIZATION OF CENTRAL SEROTONIN RECEPTORS

研究的重点是两个中枢5-HT受体（5-HT 2和5-HT 1c）， 肌醇脂质代谢，这些生理功能 受体及其调节机制。 这些问题 从基因表达的分子学研究， 受体介导的生物化学和生理学的细胞研究 对整个动物行为和生理研究的反应 功能协调发展的 具体问题是：（1）降膜的机理是什么？ 5 HT 2受体密度的调节和 拮抗剂管理？ 这些研究将集中在非典型的 抗抑郁药-5HT拮抗剂米安色林。 （二）、 是什么关系 5-HT 2行为敏感性和双重调节机制之间的关系 （5 HT 2受体识别位点和5 HT 2介导的PI中的变化） 水解）。 这些研究将比较两种生化指标， 5 HT 2受体状态具有独特的行为模式， 对功能相关5 HT 2的变化双向敏感 受体。 (3)失神经支配失败的原因是什么？ 引起，5 HT 2受体上调和反应性增加？ 一 工作假设是，神经元和神经胶质细胞上的5 HT 2受体受到调节， 通过不同的机制掩盖了神经元5 HT 2的适应性变化， 受体的 (4)5 HT 1c受体的生理作用是什么？ 的 工作假设是5 HT 1c受体介导5 HT的营养作用。 5-HT诱导脉络丛上皮细胞蛋白质合成增加 原代培养的细胞将用作模型。 (5)5 HT 1C怎么样 受体调节？ 激动剂诱导的亚敏感性机制和 将探讨拮抗剂诱导的下调，包括可能的 对5 HT 1c受体基因表达的影响。 所有这些工作背后的关键概念是， 细胞和组织中的生物化学研究与细胞和组织中的功能有关。 活生生的动物 这一办法对于实现《公约》的目标至关重要。 最终目标是弥合实验室研究之间的差距， 精神药物和精神疾病的临床治疗。

The focus in on two central 5HT receptor (5HT2 and 5HT1c) that are coupled to inositol lipid metabolism, the physiological functions of these receptors and the mechanisms by which they are regulated. These problems will be addressed at all levels, from molecular studies of gene expression to cellular studies of receptor-mediated biochemical and physiological responses to whole animal studies of behavioral and physiological functions. Specific questions are: (1) What is the mechanism of the down- regulation of 5HT2 receptor density and loss of responsiveness after antagonist administration? These studies will focus on the atypical antidepressant - 5HT antagonist, mianserin. (2). What is the relationship between 5HT2 behavioral sensitivity and the dual regulatory mechanisms (changes in 5HT2 receptor recognition site and in 5HT2-mediated PI hydrolysis). These studies will compare the two biochemical measures of the 5HT2 receptor state with a unique behavioral model that is bidirectionally sensitive to changes in functionally relevant 5HT2 receptors. (3) What is the explantation for the failure of denervation to elicit, 5HT2 receptor up-regulation and increased responsiveness? A working hypothesis is that 5HT2 receptors on neurons and glia are regulated by distinct mechanisms that mask adaptive changes in neuronal 5HT2 receptor. (4) What is the physiological role of 5HT1c receptors? The working hypothesis is that 5HT1c receptors mediate a trophic effect of 5HT. 5HT-induced elevation of protein synthesis in choroid plexus epithelial cells in primary culture will be used as a model. (5) How are 5HT1c receptors regulated? The mechanism of agonist-induced subsensitivity and of antagonist-induced down-regulation will be explored, including possible effects on the expression of the 5HT1c receptor gene. The key concept that underlies all of this work that it is imperative that biochemical studies in cells and tissues be related to function in the living animal. This approach is essential to the attainment of the ultimate goal of bridging the gap between laboratory studies of psychoactive drugs and clinical treatment of mental illness.