NEW METHOD FOR STUDYING DRUG SELF ADMINISTRATION IN MICE

跨NIH老鼠倡议目前正在进行中，目的是开发新的、 经济高效、高通量的表型分析技术，用于评估特定的 实验室近交系的中枢神经系统功能成分 老鼠。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 会被促进，大脑的基本过程和疾病的中央 神经系统将得到更好的理解和治疗。无数次的鼠标击倒 现在已经存在，但对它们的功能意义知之甚少 改变了基因。在Trans-NIH中有许多令人感兴趣的复杂行为 老鼠倡议；其中包括认知、学习和记忆，以及 以及寻求滥用药物。这项研究的目标是开发一种新的 可长期用于近交系和自交系的可卡因自我给药方法 模拟人类全部行为的小鼠基因敲除品系 或与吸毒成瘾有关的经历。其中包括收购， 维持、消灭和恢复寻找毒品和吸毒行为 行为。目前的提案试图开发一种可卡因的方法 自我给药，即离散剂量的雾化可卡因是 在鼻子戳响应之后间歇性地传送到嗅探端口，因此 避免了以前方法施加的许多限制。一共有三个 实现这一目标的具体目标：(1)设计一种能够 可靠地在间歇性地提供离散剂量的雾化可卡因 基础；(2)开发和验证这种可卡因的吸入方法 在近交系小鼠中通过训练小鼠到鼻杆进行自我给药 通过改变吸入性可卡因的剂量和 获得它所需的响应要求；(3)将此方法应用于 研究一氧化氮对近交系和基因敲除小鼠的影响 氧化合酶缺乏症的获得、维持、消退和 可卡因寻找和可卡因自我给药在神经元的恢复 一氧化氮合酶基因敲除小鼠和近交系小鼠在一氧化氮合酶抑制剂治疗后。

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.