Simpson Eleanor H, Kellendonk Christoph
Departments of Psychiatry, Columbia University, New York, New York; Center for Neurobiology and Behavior, New York State Psychiatric Institute, New York, New York.
Pharmacology, Columbia University, New York, New York; Division of Molecular Therapeutics (CK), New York State Psychiatric Institute, New York, New York.
Biol Psychiatry. 2017 Jan 1;81(1):21-30. doi: 10.1016/j.biopsych.2016.07.004. Epub 2016 Jul 14.
The dopamine hypothesis of schizophrenia is supported by a large number of imaging studies that have identified an increase in dopamine binding at the D receptor selectively in the striatum. We review a decade of work using a regionally restricted and temporally regulated transgenic mouse model to investigate the behavioral, molecular, electrophysiological, and anatomical consequences of selective D receptor upregulation in the striatum. These studies have identified new and potentially important biomarkers at the circuit and molecular level that can now be explored in patients with schizophrenia. They provide an example of how animal models and their detailed level of neurobiological analysis allow a deepening of our understanding of the relationship between neuronal circuit function and symptoms of schizophrenia, and as a consequence generate new hypotheses that are testable in patients.
精神分裂症的多巴胺假说得到了大量影像学研究的支持，这些研究发现纹状体中D受体的多巴胺结合选择性增加。我们回顾了十年的研究工作，该研究使用区域受限且时间调控的转基因小鼠模型，来研究纹状体中选择性D受体上调的行为、分子、电生理和解剖学后果。这些研究在回路和分子水平上确定了新的、可能重要的生物标志物，现在可以在精神分裂症患者中进行探索。它们提供了一个例子，说明动物模型及其详细的神经生物学分析水平如何加深我们对神经元回路功能与精神分裂症症状之间关系的理解，并因此产生可在患者中进行测试的新假说。
