Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. Dopamine is an important catecholaminergic neurotransmitter that controls movement, reward, motivation, and cognition. Recently, dopamine receptors were reported to regulate immune system in both periphery and central nervous system. However, whether dopamine D1 receptor (DRD1) activation could improve neuroinflammation in AD conditions remains unknown. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a potent and selective DRD1 agonist A-68930 on Aβ_1-42-induced mice. Here we showed that intraperitoneal injection of A-68930 significantly ameliorated Aβ_1–42-induced cognitive dysfunction in mice. Moreover, both in vivo and in vitro data showed that A-68930-induced DRD1 activation significantly inhibited NLRP3 inflammasome-dependent neuroinflammation induced by Aβ_1–42, and this effect may be mediated by the activation of AMPK/autophagy signaling pathway, which enhanced NLRP3 inflammasome degradation and thus decreased the secretion of IL-1β and IL-18. The present study suggests that A-68930-induced DRD1 signaling efficiently alleviates Aβ_1–42-induced cognitive impairment and neuroinflammation in mice and BV2 cells, and DRD1 may become a promising therapeutic target for AD.

阿尔茨海默氏病（AD）是一种不可逆的神经退行性疾病，其特征是进行性认知功能障碍和记忆障碍。多巴胺是一种重要的儿茶酚胺能神经递质，可控制运动，奖励，动机和认知。最近，据报道多巴胺受体调节周围和中枢神经系统的免疫系统。然而，多巴胺D1受体（DRD1）的激活是否可以改善AD条件下的神经炎症仍然未知。本研究旨在研究有效和选择性的DRD1激动剂A-68930对_Aβ1-42诱导的小鼠的治疗作用和潜在机制。在这里，我们显示了腹膜内注射A-68930可显着改善_Aβ1–42引起的小鼠认知功能障碍。此外，体内和体外数据均显示，A-68930诱导的DRD1活化可显着抑制_Aβ1–42诱导的NLRP3炎性体依赖性神经炎症，这种作用可能是由AMPK /自噬信号通路的活化所介导的。 NLRP3炎性体降解，因此减少了IL-1β和IL-18的分泌。本研究表明，A-68930诱导的DRD1信号传导可有效缓解_Aβ1–42诱导的小鼠和BV2细胞的认知障碍和神经炎症，而DRD1可能成为有希望的AD治疗靶点。