Centre for Addiction and Mental Health, University of Toronto Toronto, ON, Canada.
Front Neuroanat. 2011 May 31;5:31. doi: 10.3389/fnana.2011.00031. eCollection 2011.
Dopaminergic signaling within the basal ganglia has classically been thought to occur within two distinct neuronal pathways; the direct striatonigral pathway which contains the dopamine D1 receptor and the neuropeptides dynorphin (DYN) and substance P, and the indirect striatopallidal pathway which expresses the dopamine D2 receptor and enkephalin (ENK). A number of studies have also shown, however, that D1 and D2 receptors can co-exist within the same medium spiny neuron and emerging evidence indicates that these D1/D2-coexpressing neurons, which also express DYN and ENK, may comprise a third neuronal pathway, with representation in both the striatonigral and striatopallidal projections of the basal ganglia. Furthermore, within these coexpressing neurons it has been shown that the dopamine D1 and D2 receptor can form a novel and pharmacologically distinct receptor complex, the dopamine D1-D2 receptor heteromer, with unique signaling properties. This is indicative of a functionally unique role for these neurons in brain. The aim of this review is to discuss the evidence in support of a novel third pathway coexpressing the D1 and D2 receptor, to discuss the potential relevance of this pathway to basal ganglia signaling, and to address its potential value, and that of the dopamine D1-D2 receptor heteromer, in the search for new therapeutic strategies for disorders involving dopamine neurotransmission.
基底神经节中的多巴胺能信号传递传统上被认为发生在两个不同的神经元通路中；直接纹状体-苍白球通路包含多巴胺 D1 受体和神经肽强啡肽（DYN）和 P 物质，以及间接纹状体-苍白球通路，表达多巴胺 D2 受体和脑啡肽（ENK）。然而，许多研究还表明，D1 和 D2 受体可以存在于同一中间神经元中，并且新出现的证据表明，这些表达 D1/D2 的神经元，也表达 DYN 和 ENK，可能构成第三种神经元通路，存在于基底神经节的纹状体-苍白球投射和纹状体-苍白球投射中。此外，在这些共表达神经元中已经表明，多巴胺 D1 和 D2 受体可以形成一种新型的、具有独特药理学特征的受体复合物，即多巴胺 D1-D2 受体异源二聚体，具有独特的信号转导特性。这表明这些神经元在大脑中具有独特的功能作用。本综述的目的是讨论支持新型共表达 D1 和 D2 受体的第三条通路的证据，讨论该通路对基底神经节信号传递的潜在相关性，并探讨其潜在价值，以及多巴胺 D1-D2 受体异源二聚体在寻找涉及多巴胺神经传递的疾病的新治疗策略中的价值。
