FUNCTIONAL MAGNETIC RESONANCE IMAGING

在项目3中，我们建议使用大鼠模型来表征神经 可卡因诱导的功能磁共振信号改变的底物。一只动物 模型是必需的，因为使用的侵入性方法不能应用于 人类受试者。拟议中的实验将表征 构成功能性核磁共振信号的潜在生物过程， 包括对因下列直接影响而产生的贡献的分析 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fMRI信号的突触后相关性 通过将fMRI获得的大脑区域激活模式与 即刻早期基因c-fos和c-fos的原位杂交 Zif268。我们之所以提出这种方法，是因为IEG归纳的映射是 目前研究电路的最佳神经解剖学工具， 细胞和神经递质受体参与可卡因的作用。在……里面 此外，我们建议确定可卡因诱导的基本机制 FMRI和IEG都是通过一系列研究得出的，其中单胺类药物 可卡因作用的系统会受到损害。建议进行的实验 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生物学意义的假说 由可卡因管理部门生产。同时，它应该生产 关于可卡因依赖的神经基础的重要数据。

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.