FUNCTIONAL STUDIES OF BIOGENIC AMINES

描述：本研究的主要目的是更好地了解 生物胺的体内功能和调节生物胺的因子 这些路径在一个简单的模型系统。 这些路径是巨大的 对人类生物学、运动障碍和成瘾状态的重要性。 我们 有证据表明， 通过影响脊椎动物多巴胺受体的药物在果蝇中诱导 相对于它们在脊椎动物中的功能后果。 这些 行为可以诱导在断头成年苍蝇，由直接 将药物应用于神经索，也应用于活体苍蝇， 接触可卡因一种间接兴奋剂 具体目标包括：（1）遗传 选择参与可卡因反应的基因，选择 改变的可卡因抗性，以及对 重复低剂量暴露。 这些基因的分离将阐明 参与这些过程的生物途径;（2）表征 胺途径作为性别的函数被调节的机制， 主观时间和可卡因致敏。 这些研究将 为理解aim 1中分离的突变体如何导致 改变的胺能功能;（3）识别脑特异性 Ddc基因的顺式调控元件。 利用这些元素， 可能确定特定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.