Effects of Drug Use and Cessation on Monkey Brain

描述(申请人提供)：人体研究表明，可卡因依赖影响脑白质的微观结构，可能是由于药物的血管收缩作用所致。然而，关于白质损伤的时间发展和依赖期间脑血管系统的变化，或者随着药物使用的停止，两者的恢复情况，人们知之甚少。磁共振成像(MRI)提供了非常适合于以非侵入性方式研究大脑的解剖、结构、功能和化学特征的工具。在这项应用中，我们建议使用一套MRI技术来研究使用可卡因对猴子大脑的影响，特别是它对大脑灰质/白质体积的白质微结构、对灰质和白质的血管和灌流的影响以及对猴子大脑的神经化学特征的影响。这些技术将被用于对一小群控制良好的猴子进行初步研究。目的1.建立一种稳健的方法来研究猴脑的结构、解剖和功能测量。目的2.收集药物使用及戒毒对猴脑影响的初步数据。我们的假设是：1.长期服用可卡因会导致猴子大脑的变化，与人类研究中看到的类似。2.停止使用药物将导致大脑测量正常化。这将解决一个重要的问题，即在停止使用药物后是否有显著的大脑恢复。

DESCRIPTION (provided by applicant): Human studies show that cocaine dependence affects the microstructure of white matter, probably as a result of vasoconstrictive effects of the drug. Little is known, however, about the temporal development of the white matter injury and the changes in cerebral vasculature during the dependence period, or about the recovery of both with cessation of the drug use. Magnetic resonance imaging (MRI) provides tools that are highly suitable for investigating in a non-invasive manner the anatomical, structural and functional and chemical characteristics of the brain. In this application we propose to implement a set of MRI techniques for investigating the effects of the use of cocaine on monkey brain, in particular its effects on white matter microstructure on gray/white matter volumes, on the vascularity and perfusion of gray and white matter and on the neurochemical profile of the monkey brain. These techniques will be used to perform a preliminary study on a small and well-controlled population of monkeys. Aim 1. To develop a robust methodology for investigating structural, anatomical and functional measures in monkey brains. Aim 2. To collect preliminary data on the effects of drug use and its cessation on monkey brain. We hypothesize that: 1. Long term cocaine self-administration will result in brain changes in the monkeys similar to those seen in human studies. 2. Cessation of drug use will result in a normalization of brain measures. This will address the important issue of whether or not there is significant brain recovery following cessation of drug use.