FUNCTIONAL STUDIES OF BIOGENIC AMINES

描述：这项研究的广泛目标是更好地了解 生物胺的体内功能及其调节因素 这些路径在一个简单的模型系统中。这些小路是巨大的 对人类生物学、运动障碍和上瘾状态的重要性。我们 有证据表明，行为的类型具有显著的保守性 在果蝇中被影响脊椎动物多巴胺受体的药物诱导 相对于它们在脊椎动物身上的功能后果。这些 在被斩首的成年果蝇身上都可以通过直接的 将药物应用于神经索，也适用于活的苍蝇，通过 接触可卡因，一种间接的激动剂。具体目标包括(1)遗传 选择与可卡因反应有关的基因，选择 改变对可卡因的抵抗力，以及对 反复低剂量暴露。分离这些基因将阐明 参与这些过程的生物途径；(2)表征 胺通路作为性别的函数被调节的机制， 主观一天的时间和可卡因的敏化。这些研究将 为了解在目标1中分离的突变体是如何领先的提供了基础 改变胺能功能；(3)脑特异性鉴定 DDC基因的顺式调控元件。使用这些元素，它将成为 有可能确定特定的胺能细胞的行为作用 集群。

DESCRIPTION: The broad objectives of this study are to better understand the in vivo functioning of biogenic amines and the factors that modulate these pathways in a simple model system. These pathways are of enormous importance to human biology, movement disorders, and addictive states. We have evidence for a striking conservation in the types of behaviors that can be induced in flies by drugs affecting vertebrate dopamine receptors relative to their functional consequences in vertebrate animals. These behaviors can be induced both in decapitated adult flies, by direct application of drugs to the nerve cord, and also in living flies, by exposure to cocaine, an indirect agonist. Specific aims include (1) genetic selection for genes involved in cocaine responsiveness, selecting for altered cocaine resistance, and resistance to the sensitizing effects of repeated low dose exposure. Isolation of these genes will elucidate the biological pathways involved in these processes; (2) characterization of the mechnisms by which the amine pathways are modulated as a function of sex, time of subjective day, and cocaine sensitization. These studies will provide the basis for understanding how the mutants isolated in aim 1 lead to altered aminergic function; (3) identification of brain specific cis-regulatory elements of the Ddc gene. Using these elements, it will be possible to determine the behavioral roles of specific aminergic cell clusters.