Voltammetry in Freely Moving Mice

描述(由申请人提供)： 分子生物学的进步，包括创造转基因小鼠，对成瘾研究产生了巨大的影响。许多小鼠品系对可卡因和其他滥用药物的反应性发生了变化，为药物作用的初始作用部位和下游贡献者提供了信息来源。一种强大的生物传感器技术，快速扫描循环伏安法，最近被应用于自由活动大鼠的多巴胺(DA)和其他单胺类神经递质的测量，我们建议建立这种技术用于自由活动的小鼠。这将允许在没有麻醉干扰的情况下，对大脑电路完整的小鼠进行DA监测。此外，最新、最先进类型的伏安记录是在没有任何电刺激的情况下自发释放DA。这些测量是DA系统活动的真实反映，这将极大地有助于确定可卡因和其他滥用药物如何改变DA功能。DA“尖峰”，或DA的快速波动，被认为是由于DA神经元的同步放电，提供了一种比使用电刺激更少人为地检查DA系统活动的方法。这项应用的重点是两项技术创新：1)在自由活动的小鼠中使用伏安法，2)记录自发的DA峰。这些测量在未来的成瘾研究中有很多应用，例如，包括监测其他神经递质，以及使用基因改变或重组近亲交配的小鼠品系。

DESCRIPTION (provided by applicant): Advances in molecular biology, including the creation of genetically altered mice, have had a tremendous impact on addiction research. Many mouse strains show altered responsiveness to cocaine and other abused drugs, providing a source of information on initial sites of action and downstream contributors to the effects of drugs. A powerful biosensor technique, fast-scan cyclic voltammetry (voltammetry), has recently been applied to the measurement of dopamine (DA) and other monoamine neurotransmitters in freely moving rats, and we propose to establish this technique for use in freely moving mice. This will allow monitoring of DA in mice with intact brain circuitry without the interference of anesthesia. In addition, the newest, state-of-the-art types of voltammetric recordings are of spontaneous DA release without any electrical stimulation. These measurements are true reflections of DA system activity that will be immensely helpful in determining how DA function is altered by cocaine and other abused drugs. DA "spikes", or rapid fluctuations of DA, are thought to be due to synchronous firing of DA neurons and provide a less artificial way of examining DA system activity than using electrical stimulation. The focus of this application is on two technical innovations: 1) use of voltammetry in freely moving mice and 2) recording spontaneous DA spikes. There are many applications of these measurements to addiction research in the future, including, for example, monitoring other neurotransmitters and using genetically altered or recombinant inbred mouse strains.