A GENETIC STUDY OF DROSOPHILA RESPONSES TO COCAINE

果蝇对可卡因反应的基因研究

• 批准号: 6378328
• 负责人: ROLAND J BAINTON
• 金额: $ 16.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-20 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378328
• 关键词: Drosophilidae; behavior test; crack cocaine; gene complementation; genetic screening; molecular cloning; mutant; pharmacogenetics; psychopharmacology; transposon /insertion element

The central nervous system effects of many neruropharmaceuticals and in particular the action of addictive drugs is only partially understood. We propose to develop a system that uses the acute behavioral responses of Drosophila to study addictive drugs, specifically "crack" cocaine. Acute behavioral responses to cocaine in flies have similarities to those in vertebrates. We have a behavioral assay for rapid assessment of acute sensitivity to vaporized free base cocaine. Drosophila has a highly developed genetic system which provides many tools that make facile a forward genetic screen for altered sensitivity to drug responses. The aims of this proposal are: 1) to isolate mutants that respond abnormally to the acute stimulant properties of cocaine; 2) to develop secondary assays that refine our selection of mutants to those most pertinent to the stimulant- induced effects of cocaine; 3) to clone and characterize genes that modulate these behavioral responses in flies. Our genetic analysis should yield tools for the study of the molecular and biochemical mechanisms that underlie stimulant induced responses.

许多神经药物的中枢神经系统作用，特别是成瘾药物的作用，人们只了解了一部分。我们建议开发一种系统，利用果蝇的急性行为反应来研究成瘾药物，特别是“可卡因”。果蝇对可卡因的急性行为反应与脊椎动物的相似。我们有一种快速评估蒸发游离基可卡因急性敏感性的行为测试方法。果蝇有一个高度发达的遗传系统，它提供了许多工具，使易捷成为对药物反应改变敏感性的前向遗传筛查。这项建议的目的是：1)分离对可卡因的急性刺激特性做出异常反应的突变体；2)开发二次测试，以精炼我们对与可卡因的刺激剂诱导的效应最相关的突变体的选择；3)克隆和表征调节果蝇这些行为反应的基因。我们的遗传分析应该为研究刺激诱导反应背后的分子和生化机制提供工具。