Sokoloff P, Diaz J, Le Foll B, Guillin O, Leriche L, Bezard E, Gross C
INSERM, Unité de Neurobiologie et Pharmacologie, Moléculaire (U573), Centre Paul Broca, 2ter rue d'Alésia, 75014 Paris, France.
CNS Neurol Disord Drug Targets. 2006 Feb;5(1):25-43. doi: 10.2174/187152706784111551.
The role of the D(3) receptor has remained largely elusive before the development of selective research tools, such as selective radioligands, antibodies, various highly specific pharmacological agents and knock-out mice. The data collected so far with these tools have removed some of the uncertainties regarding the functions mediated by the D(3) receptor. The D(3) receptor is an autoreceptor that controls the phasic, but not tonic activity of dopamine neurons. The D(3) receptor, via regulation of its expression by the brain-derived neurotrophic factor (BDNF), mediates sensitization to dopamine indirect agonists. This process seems responsible for side-effects of levodopa (dyskinesia) in the treatment of Parkinson's disease (PD), as well as for some aspects of conditioning to drugs of abuse. The D(3) receptor mediates behavioral abnormalities elicited by glutamate/NMDA receptor blockade, which suggests D(3) receptor-selective antagonists as novel antipsychotic drugs. These data allow us to propose novel treatment options in PD, schizophrenia and drug addiction, which are awaiting evaluation in clinical trials.
在选择性研究工具（如选择性放射性配体、抗体、各种高特异性药理试剂和基因敲除小鼠）出现之前，D(3)受体的作用在很大程度上一直难以捉摸。到目前为止，使用这些工具收集的数据消除了一些关于D(3)受体介导功能的不确定性。D(3)受体是一种自身受体，可控制多巴胺神经元的时相性而非紧张性活动。D(3)受体通过脑源性神经营养因子（BDNF）对其表达的调节，介导对多巴胺间接激动剂的敏化作用。这一过程似乎是帕金森病（PD）治疗中左旋多巴副作用（运动障碍）的原因，也是药物成瘾某些方面的条件作用的原因。D(3)受体介导由谷氨酸/NMDA受体阻断引起的行为异常，这表明D(3)受体选择性拮抗剂可作为新型抗精神病药物。这些数据使我们能够提出针对PD、精神分裂症和药物成瘾的新型治疗方案，这些方案有待在临床试验中进行评估。
