Marsden Charles A
School of Biomedical Sciences, Institute of Neuroscience, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH.
Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S136-44. doi: 10.1038/sj.bjp.0706473.
Dopamine has moved from being an insignificant intermediary in the formation of noradrenaline in 1957 to its present-day position as a major neurotransmitter in the brain. This neurotransmitter is involved in the control of movement and Parkinson's disease, the neurobiology and symptoms of schizophrenia and attention deficit hyperactivity disorder. It is also considered an essential element in the brain reward system and in the action of many drugs of abuse. This evolution reflects the ability of several famous names in neuropharmacology, neurology and psychiatry to apply new techniques to ask and answer the right questions. There is now excellent knowledge about the metabolism of dopamine, dopamine receptor systems and the structural organisation of dopamine pathways in the brain. Less is known about the function of the different receptors and how the various dopamine pathways are organised to produce normal behaviour, which exhibits disruption in the disease states mentioned. In particular, we have very limited information as to why and how the dopamine system dies or becomes abnormal in Parkinson's disease or a neurodevelopmental disorder such as schizophrenia. Dopamine neurones account for less than 1% of the total neuronal population of the brain, but have a profound effect on function. The future challenge is to understand how dopamine is involved in the integration of information to produce a relevant response rather than to study dopamine in isolation from other transmission systems. This integrated approach should lead to greater understanding and improved treatment of diseases involving dopamine.
多巴胺已从1957年在去甲肾上腺素形成过程中微不足道的中间体,转变为如今大脑中的主要神经递质。这种神经递质参与运动控制以及帕金森病、精神分裂症和注意力缺陷多动障碍的神经生物学及症状。它还被认为是大脑奖赏系统以及许多滥用药物作用中的关键要素。这一演变反映了神经药理学、神经病学和精神病学领域几位知名人士运用新技术提出并回答正确问题的能力。目前,人们对多巴胺的代谢、多巴胺受体系统以及大脑中多巴胺通路的结构组织已有深入了解。对于不同受体的功能以及各种多巴胺通路如何组织以产生正常行为,而这些行为在上述疾病状态中会出现紊乱,我们了解得较少。特别是,关于帕金森病或精神分裂症等神经发育障碍中多巴胺系统为何以及如何死亡或变得异常,我们掌握的信息非常有限。多巴胺神经元在大脑神经元总数中所占比例不到1%,但对功能有深远影响。未来的挑战是了解多巴胺如何参与信息整合以产生相关反应,而不是孤立地研究多巴胺与其他传递系统。这种综合方法应能增进对涉及多巴胺的疾病的理解并改善治疗。