Alcohol preference in zebra fish: a novel paradigm

斑马鱼的酒精偏好：一种新的范例

• 批准号: 7127710
• 负责人: Robert T. Gerlai
• 金额: $ 12.52万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127710
• 关键词: alcoholism /alcohol abuse; automated data processing; avoidance behavior; behavior test; behavioral /social science research tag; behavioral genetics; computer system design /evaluation; conditioning; data collection methodology /evaluation; disease /disorder model; ethanol; genetic screening; method development; monitoring device; mutagens; nitrosourea; point mutation; preference; psychomotor function; substance abuse related behavior; zebrafish

DESCRIPTION Alcohol abuse is one of the most devastating and costly diseases. Its mechanisms are not well understood and effective treatment is lacking. One way to study this complex disease is with the use of model organisms. Zebra fish (Danio rerio) may be a useful model system with which the mechanisms of acute and chronic effects of alcohol can be investigated. However, high throughput behavioral tests allowing fast screening of alcohol related functional alterations of the brain of zebra fish (or tests allowing quick detection of neurobiological changes induced by mutations of genes associated with alcohol related mechanisms) are almost completely unavailable. The goal of the proposal is to develop such behavioral paradigms. A novel Y-tank system will be designed in which zebra fish will swim against a slow water current and choose between the left or right goal arms of the tank. The paradigm is versatile and will enable us to test motor function, alcohol preference/avoidance, and alcohol rewarded place preference. Quantification of behavior hi the test will be automated with the use of infrared photocell detectors feeding the behavioral data to computers that will monitor and record the behavioral responses as well as control the delivery of stimuli (e.g., alcohol and conditioned stimuli). Automation will allow us to increase the number of apparati running in parallel thus making the system useful for high throughput screening. Ultimately, we will use the paradigm to screen and identify mutant zebra fish generated by random mutagenesis (ethyl-nitroso-urea or ENU induced point mutations), a forward genetic approach that will lead to the identification of genes involved in acute and chronic alcohol related behaviors. Zebra fish is particularly appropriate as a model organism for our purpose because of its small size, prolific nature (200+ fish per spawning), ease of controlling of its environment, ease of delivery of water soluble substances such as alcohol (fish absorb it through their gills and skin), and the huge amount of genetic information and genetic tools available. As several genes discovered in zebra fish show high homology to human, we hope the proposed studies will facilitate the unraveling of the mechanisms of acute and chronic alcohol effects in human ultimately resulting in the development of efficient treatments.

描述酒精滥用是最毁灭性和昂贵的疾病之一。它的机制尚不清楚，缺乏有效的治疗方法。研究这种复杂疾病的一种方法是使用模型生物。斑马鱼（Danio Rerio）可能是一个有用的模型系统，可以研究酒精的急性和慢性作用的机制。但是，高通量行为测试，允许快速筛选斑马鱼大脑的功能改变（或允许快速检测与与酒精相关机制相关的基因突变引起的神经生物学变化的测试）几乎完全不可用。该提案的目的是开发这种行为范式。将设计一个新颖的Y tank系统，其中斑马鱼会在慢速水流上游泳，并在水箱的左门或右射线臂之间进行选择。该范式具有多功能性，将使我们能够测试运动功能，酒精偏好/避免以及奖励酒精奖励的地方偏好。行为HI的量化将通过使用红外光电检测器来自动化测试，从而将行为数据馈送到计算机，以监测和记录行为响应，并控制刺激的传递（例如，酒精和条件刺激）。自动化将使我们能够并行增加仪器的数量，从而使系统对高吞吐量筛查有用。最终，我们将使用范式筛选和鉴定由随机诱变产生的突变斑马鱼（乙醇 - 硝基尿素或ENU诱导点突变），这是一种正向遗传方法，将导致鉴定涉及急性和慢性酒精相关行为的基因。斑马鱼特别适合作为我们目的的模型生物，因为它的尺寸很小，多产性（每产产卵200多种），易于控制环境，易于递送水溶性物质（例如酒精（FILL）（鱼通过其g和皮肤吸收）以及可用的大量遗传信息和遗传工具。正如斑马鱼中发现的几个基因与人类的同源性很高，我们希望拟议的研究将促进人类急性和慢性酒精作用的机制最终导致有效治疗的发展。