Dopamine D2 autoreceptors (D₂ARs), located in somatodendritic and axon terminal compartments of dopamine (DA) neurons, function to provide a negative feedback regulatory control on DA neuron firing, DA synthesis, reuptake and release. Dysregulation of D₂AR-mediated DA signaling is implicated in vulnerability to substance use disorder (SUD). Due to the extreme low abundance of D₂ARs compared to postsynaptic D₂ receptors (D₂PRs) and the lack of experimental tools to differentiate the signaling of D₂ARs from D₂PRs, the regulation of D₂ARs by drugs of abuse is poorly understood. The recent availability of conditional D₂AR knockout mice and newly developed virus-mediated gene delivery approaches have provided means to specifically study the function of D₂ARs at the molecular, cellular and behavioral levels. There is a growing revelation of novel mechanisms and new proteins that mediate D₂AR activity, suggesting that D₂ARs act cooperatively with an array of membrane and intracellular proteins to tightly control DA transmission. This review highlights D₂AR-interacting partners including transporters, G-protein-coupled receptors, ion channels, intracellular signaling modulators, and protein kinases. The complexity of the D₂AR interaction network illustrates the functional divergence of D₂ARs. Pharmacological targeting of multiple D₂AR-interacting partners may be more effective to restore disrupted DA homeostasis by drugs of abuse.

多巴胺 D2 自身受体 (D ₂ AR) 位于多巴胺 (DA) 神经元的体细胞树突和轴突末端区室中，其功能是对 DA 神经元放电、DA 合成、再摄取和释放提供负反馈调节控制。D ₂ AR 介导的 DA 信号传导失调与物质使用障碍 (SUD) 的脆弱性有关。_{由于与突触后 D 2}受体 (D ₂ PR)相比，D 2 AR_的丰度极低，并且缺乏区分 D ₂ AR 和 D ₂ PR 信号传导的实验工具，滥用药物对 D ₂ AR的调节人们对此知之甚少。最近出现的条件性 D ₂ AR 敲除小鼠和新开发的病毒介导的基因传递方法为在分子、细胞和行为水平上专门研究 D _{2 AR 的功能提供了手段。}越来越多的新机制和新蛋白质介导 D ₂ AR 活性，表明 D ₂ AR 与一系列膜和细胞内蛋白质协同作用，严格控制 DA 传输。本综述重点介绍了 D ₂ AR 相互作用伙伴，包括转运蛋白、G 蛋白偶联受体、离子通道、细胞内信号调节剂和蛋白激酶。D _{2 AR 交互网络的复杂性说明了 D 2} AR的功能分歧。多个 D ₂ AR 相互作用伙伴的药理学靶向可能更有效地恢复滥用药物所破坏的 DA 稳态。