Schloesser R, Simkowitz P, Bartlett E J, Wolkin A, Smith G S, Dewey S L, Brodie J D
Department of Psychiatry, New York University Medical Center 10016, USA.
Clin Neuropharmacol. 1996 Oct;19(5):371-89. doi: 10.1097/00002826-199619050-00001.
Functional brain imaging with positron emission tomography (PET) has opened up new avenues for the investigation of possible functional disturbances related to psychiatric disease as well as pharmacodynamic assessment of drug treatment in vivo. Different strategies to study pharmacologic effects on the brain have been developed in recent years. The basic methods are to measure (a) blood flow or glucose metabolism, (b) parameters of specific receptor binding, or (c) neurotransmitter metabolism. Each of these can be performed either in a resting state or after perturbation with a pharmacologic challenge. Our group has developed a general strategy for investigating pharmacologic effects on brain function: (a) determining indirect drug-induced metabolic changes with fluorodeoxyglucose PET and (b) characterizing functional interactions of neurotransmitter systems by assaying drug-induced displacement of specific receptor ligands. These study designs reflect a paradigm shift where functional coupling of brain regions and interaction of different neurotransmitter systems are seen as the basis for a multitransmitter hypothesis of schizophrenia. In this view, any disturbance in the self-regulatory process is reflected in the loss of functional interaction between systems. An overview of recent studies and their possible clinical importance will be presented.
正电子发射断层扫描（PET）的功能性脑成像为研究与精神疾病相关的可能功能障碍以及体内药物治疗的药效学评估开辟了新途径。近年来，已开发出不同的研究大脑药理作用的策略。基本方法是测量：（a）血流或葡萄糖代谢；（b）特定受体结合参数；或（c）神经递质代谢。这些方法中的每一种都可以在静息状态下或在药理学激发扰动后进行。我们小组已经开发出一种研究大脑功能药理作用的通用策略：（a）用氟脱氧葡萄糖PET确定间接药物诱导的代谢变化；（b）通过检测药物诱导的特定受体配体置换来表征神经递质系统的功能相互作用。这些研究设计反映了一种范式转变，即脑区的功能耦合和不同神经递质系统的相互作用被视为精神分裂症多递质假说的基础。按照这种观点，自我调节过程中的任何干扰都反映在系统之间功能相互作用的丧失上。本文将概述近期的研究及其可能的临床重要性。
