FUNCTIONAL MAGNETIC RESONANCE IMAGING

在项目3中，我们建议使用大鼠模型来表征神经系统的功能。 可卡因诱导的fMRI信号改变的底物。 动物 模型是必需的，因为所使用的侵入性方法不能应用于 人类实验对象 拟议的实验将表征 对功能磁共振成像信号有贡献的潜在生物过程， 包括对下列因素的直接影响所产生的贡献的分析： 可卡因对血管的作用与其对靶神经元的直接作用。 我们 然后计划研究功能磁共振成像信号的突触后相关性， 通过比较功能磁共振成像获得的局部大脑激活模式， 立即早期基因（IEGs）c-fos和 zif268. 我们提出这种方法，因为IEG感应的映射是 目前最好的功能性神经解剖学工具来研究电路， 细胞和参与可卡因作用的神经递质受体。 在 此外，我们建议确定可卡因诱导的基本机制， 一系列的研究表明，功能磁共振成像和IEG的“信号”， 可卡因作用的系统会受到损害。 提出的实验 直接影响我们对人类数据的解释 在项目1中获得。 项目3旨在严格测试 关于功能磁共振信号的生物学意义的假说 由可卡因引起的。 与此同时， 关于可卡因依赖的神经基质的重要数据。

In Project 3, we propose to use a rat model to characterize the neural substrates of cocaine-induced alterations in fMRI signals. An animal model is required because the invasive methods used cannot be applied to human subjects. The proposed experiments will characterize the underlying biological processes that contribute to the fMRI signal, including an analysis of contributions due to the direct effects of cocaine on the vascular versus its direct effects on target neurons. We then plan to investigate the postsynaptic correlates of the fMRI signal by comparing patterns of regional brain activation obtained by fMRI with in situ hybridization for the immediate early genes (IEGs) c-fos and zif268. We propose this approach because mapping of IEG induction is the best current functional neuroanatomic tool to investigate circuits, cells, and neurotransmitter receptors involved in cocaine action. In addition we propose to identify basic mechanisms by which cocaine induces both fMRI and IEG 'signals' by a series of studies in which the monoamine systems acted upon by cocaine are lesioned. The experiments proposed in Project 3 directly impact our interpretation of the human data obtained in Project 1. Project 3 is designed to rigorously test hypotheses concerning the biological significance of fMRI signals produced by cocaine administration. At the same time it should produce significant data on the neural substrates of cocaine dependence.