Some brain penetrable P2X7R antagonists such as BBG and A-438079 have exhibited antidepressant effects in chronic unpredictable mild stress (CUMS) mice model of depression by inhibiting the activation of P2X7/NLRP3/IL-1β pathway (Yue et al., 2017; Bhattacharya, 2018). Here, P2RX7 is linked to major depressive disorder.