Schwarz Adam J, Gozzi Alessandro, Reese Torsten, Heidbreder Christian A, Bifone Angelo
Department of Neuroimaging, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline, Via Fleming 4, 37135 Verona, Italy.
Magn Reson Imaging. 2007 Jul;25(6):811-20. doi: 10.1016/j.mri.2007.02.017. Epub 2007 Apr 18.
Pharmacological MRI (phMRI) experiments utilise fMRI time series methods to map the central effect of pharmaceutical compounds. The typical univariate maps may, however, integrate the effects of several different neurotransmitter systems or underlying mechanisms. The results may thus be spatially and/or mechanistically nonspecific. Intersubject correlation analysis based on the phMRI response amplitude can more directly identify patterns of functional connectivity underlying the central effects of an acutely administered compound. In this article, we extend this approach to experiments where the effects of one compound in modulating the response to another are of interest. Specifically, we show a modulation of the correlation structure of a probe compound (d-amphetamine) by pretreatment with the selective dopamine D3 receptor antagonist SB277011A in the rat. The strongest modifications in the correlation patterns occurred in connection with the ventral tegmental area, the source of mesolimbic dopamine projections and a key substrate in the reward system.
药理磁共振成像（phMRI）实验利用功能磁共振成像时间序列方法来绘制药物化合物的中枢效应图谱。然而，典型的单变量图谱可能整合了几种不同神经递质系统或潜在机制的效应。因此，结果在空间和/或机制上可能是非特异性的。基于phMRI反应幅度的受试者间相关性分析可以更直接地识别急性给药化合物中枢效应背后的功能连接模式。在本文中，我们将这种方法扩展到研究一种化合物对另一种化合物反应的调节作用的实验中。具体而言，我们展示了在大鼠中，通过选择性多巴胺D3受体拮抗剂SB277011A预处理对探针化合物（d-苯丙胺）相关性结构的调节作用。相关性模式的最强改变发生在腹侧被盖区，它是中脑边缘多巴胺投射的来源，也是奖励系统中的关键底物。
