Volkow N D, Fowler J S, Gatley S J, Logan J, Wang G J, Ding Y S, Dewey S
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
J Nucl Med. 1996 Jul;37(7):1242-56.
Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson's disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors, dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of changes in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson's disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurological parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. Through the parallel development of new radiotracers, kinetic models and better instruments, PET technology is enabling investigation of increasingly more complex aspects of the human brain dopamine system. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research.
多巴胺在运动、动机和认知的调节与控制中起着关键作用。它还与奖赏、强化和成瘾密切相关。脑内多巴胺异常与许多神经和精神疾病有关，包括帕金森病、精神分裂症和药物滥用。多巴胺与神经和精神疾病以及药物滥用之间的这种紧密联系，使其成为神经科学研究中的一个重要课题，也是药物开发中的一个重要分子靶点。正电子发射断层扫描（PET）能够直接测量活体人脑中多巴胺系统的组成部分。它依赖于放射性示踪剂，这些示踪剂可标记多巴胺受体、多巴胺转运体、多巴胺前体或对降解多巴胺的酶具有特异性的化合物。此外，通过使用能够提供有关区域脑代谢或血流信息的示踪剂以及神经化学特异性药理干预，PET可用于评估脑多巴胺活性变化的功能后果。PET多巴胺测量已被用于研究正常人类大脑及其在精神和神经疾病中的作用。它还被用于精神药理学研究，以研究用于治疗帕金森病和精神分裂症的多巴胺药物，以及研究滥用药物对多巴胺系统的影响。由于可以在同一受试者中研究各种功能和神经参数，PET能够研究人脑中多巴胺系统的功能完整性以及多巴胺与其他神经递质的相互作用。通过新放射性示踪剂、动力学模型和更好仪器的并行发展，PET技术能够研究人脑中多巴胺系统越来越复杂的方面。本文总结了为用PET评估人脑中多巴胺系统的各种元素而开发的不同示踪剂和实验策略及其在临床研究中的应用。
