Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Hum Mol Genet. 2013 Apr 15;22(8):1574-80. doi: 10.1093/hmg/ddt007. Epub 2013 Jan 11.
Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging.
人脑影像学一直是理解神经精神药理学的宝贵辅助手段，特别是在纹状体中多巴胺在精神疾病中的作用。在这里，我们根据人类大脑影像学的结果报告了一项针对主要精神疾病的遗传小鼠模型的研究：一项使用小动物正电子发射断层扫描（PET）、放射自显影、微透析和分子生物学的系统研究，在一个假定的显性负 DISC1 转基因模型中。该小鼠模型显示纹状体中多巴胺 D2 受体（D2R）的放射性配体结合增加，以及对甲基苯丙胺给药的神经化学和行为变化。之前我们报道过，该模型在强迫游泳测试中表现出缺陷，这是抗抑郁功效的代表性指标。通过结合我们两项研究的结果，我们提出了一个未来研究的工作假设，即该模型可能代表抑郁和精神病的混合状态。我们希望这项研究也将有助于弥合转化精神病学中基础动物模型的特征描述和主要通过 PET 成像对患者进行临床药理学评估之间的重大差距。
