A previous study has indicated that P2X7R is up-regulated in infarcted hearts and P2X7R inhibition inhibits the activation of NF-κB and suppresses sympathetic activation in MI.49 A latest study pointed out that the ATP/P2X7 axis played an instrumental role in myocardial inflammation and hypertrophy, in which heart–brain interaction evoked sympathetic efferent nerves to release extracellular ATP, subsequently inducing hypertrophic lesions in cardiomyocytes.50 However, to our knowledge, we are the first to investigate the role of P2X7R in AF in depression models. This evidence concerns the gene NFKB1 and major depressive disorder.