NEW METHOD FOR STUDYING DRUG SELF ADMINISTRATION IN MICE

研究小鼠自我给药的新方法

• 批准号: 6225342
• 负责人: Kathleen M. Kantak
• 金额: $ 8.15万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6225342
• 关键词: biomedical equipment development; cocaine; genetic strain; genetically modified animals; inbreeding; inhalation drug administration; laboratory mouse; method development; nitric oxide synthase; self medication; substance abuse related behavior

The Trans-NIH Mouse Initiative is now underway for developing new, cost-effective, high throughput phenotyping techniques to assess specific components of central nervous system function in inbred strains of laboratory mice. One purpose for developing such techniques is to apply this technology to mutant mice; with the expectation that the genetic analysis of complex traits will be facilitated and that basic brain processes and diseases of the central nervous system will be better understood and treated. Numerous mouse knockouts now exist, but little is known regarding the functional significance of their altered genetics. There are many complex behaviors of interest in the Trans-NIH Mouse Initiative; among them are cognition, learning and memory, and the taking and seeking of drugs of abuse. The goal of this research is to develop a new method of cocaine self-administration that can be used long-term in inbred and genetic knockout strains of mice to simulate the full array of human behaviors or experiences associated with drug addiction. These include the acquisition, maintenance, extinction and reinstatement of drug-seeking and drug-taking behavior. The present proposal seeks to develop a method of cocaine self-administration whereby a discrete dose of aerosolized cocaine is intermittently delivered to a sniff port after a nose-poke response, thus avoiding many of the limitations imposed by previous methods. There are three specific aims to accomplish this goal: (1) Design an apparatus that can reliably deliver a discrete dose of aerosolized cocaine on an intermittent basis; (2) Develop and validate this inhalation method of cocaine self-administration in an inbred mouse strain by training mice to nose pole for cocaine delivery and by varying both the dose of inhaled cocaine and the response requirements necessary for obtaining it; (3) Apply this method in inbred and genetic knockout strains of mice by studying the effects of nitric oxide synthase deficiency on the acquisition, maintenance , extinction and reinstatement of cocaine-seeking and cocaine self-administration in neuronal NOS knockout mice and in inbred strains of mice after NOS inhibitor treatment.

美国国立卫生研究院小鼠计划正在开发新的， 具有成本效益的高通量表型分析技术， 实验室近交系中枢神经系统功能成分 小鼠开发这种技术的一个目的是将这种技术应用于 突变小鼠;期望复杂性状的遗传分析 将促进和基本的大脑过程和疾病的中央 神经系统将得到更好的理解和治疗。多次敲除小鼠 现在存在，但很少有人知道他们的功能意义， 改变基因在Trans-NIH中有许多感兴趣的复杂行为 小鼠主动性;其中包括认知，学习和记忆，以及服用 以及寻求滥用药物。这项研究的目的是开发一种新的 可卡因自我给药的方法，可长期用于近交系， 基因敲除小鼠品系，以模拟人类的全部行为 或与毒瘾有关的经历。其中包括收购， 觅药、吸毒的维持、消灭和复吸 行为本提案寻求开发一种可卡因的方法， 自我给药，其中分散剂量的雾化可卡因被 在鼻子戳响应之后间歇地传递到嗅探端口，因此 避免了先前方法所施加的许多限制。有三 实现这一目标的具体目标：（1）设计一种装置， 可靠地在间歇性地输送离散剂量的雾化可卡因， （2）开发并验证可卡因的吸入方法 在近交系小鼠品系中通过训练小鼠的鼻杆进行自我给药， 可卡因递送和通过改变吸入可卡因的剂量和 （3）将该方法应用于 近交系和基因敲除品系小鼠通过研究硝酸盐的影响， 一氧化碳合酶缺乏对获得、维持、灭绝和 神经元中可卡因寻求和可卡因自我给药的恢复 NOS敲除小鼠和NOS抑制剂治疗后的近交系小鼠。