多巴胺D3受体(D3R)的神经科学新进展

多巴胺(DA)是脑内一种重要的神经递质,通过不同DA受体亚型调控运动功能、认知活动和药物成瘾等生理、病理过程。多巴胺D3受体(D3R)属于D2样受体,但其功能长期不明。近年来,人们对它在神经科学中的意义有了新的认识。首先,D3R的信号通路独特,它被激活后显示细胞增殖效应,但cAMP信号传导途径不明显。其次,D3R基因敲除小鼠研究提示,正常生理状态下D3R仅表现辅助功能：在特定病理条件下,D3R显示出重要的“平衡缓冲作用”,在精神分裂症、帕金森病(PD)治疗中运动障碍副作用LID的发生和毒品复吸等病理过程扮演了重要角色。因此,D3R是一个重要的药物靶标。D3R拮抗剂在精神分裂症治疗中显示了临床前景,D3R激动剂则对PD治疗和毒品复吸防治展示了应用价值。

Advances of dopamine D3 receptor in neurobiology

Dopamine is one of important neurotransmitters in brain, and is implicated in the regulation of motor activity, cognition process and drug abuse through different dopamine receptor subtypes. The function of dopamine D3 receptor (D3R), a member of D2-like receptors, has been elusive for a long time. New advances of D3R have been achieved in recently years. Activation of D3R results in the cell mitogenesis in function assay in vitro, and the signaling pathway is not typical cAMP signal. The D3R knock-out mice have also been generated. The results from these mice show D3R plays a secondary role in physiological condition. However, the role is switched to unique "buffer action" in the pathological condition, which is premised on the prevention of various neuropsychiatric disorders such as schizophrenia, dyskinesia induced by levodopa during Parkinson's disease therapy and drug craving. Therefore, D3R is an important therapeutic target. The antagonists of D3R are supposed to improve schizophrenia, while the PD patients and drug abuser will benefit from the agonists of D3R.