Fig. 8. Focal genetic inactivation of A2AR in the lateral septum (LS) affords an anti-depressant-like phenotype.
a Left: A2AR-specific interference virus (AAV9-syn-A2ARshRNA-GFP, A2AR-shRNA) and control virus (AAV9-syn-A2ARshcontrol-GFP, ctrl-shRNA) were unilaterally injected in the LS of C57BL/6 J mice. Nuclei are stained with DAPI in blue. LS, lateral septum; MS, medial septum; NAc, Nucleus Accumbens core. Scale bar: 1000 μm. Right: The downregulation of A2AR in the LS was verified by qPCR (n = 3 and 4 mice per group for control and A2A-shRNA, respectively. Unpaired t test, p = 0.0383, t(5)=2.794). b The downregulation of A2AR reduced immobility in the tail suspension test (TST) (n = 20 and 18 mice per group for control and A2A-shRNA, respectively, Unpaired t test, p = 0.0049, t(36) = 2.995) without affecting basic motor activity (n = 20 and 18 mice per group for control and A2A-shRNA, respectively. Unpaired t test, p = 0.0860, t(36) = 1.765) and time spent in the central area (n = 20 and 18 mice per group for control and A2A-shRNA, respectively. Mann–Whitney test, p = 0.1645, U = 132) in the open field test (OFT) (c, d). e, f Mice subject to LS-A2AR knockdown displayed a similar total liquid consumption (n = 9 mice/group, Unpaired t test, p = 0.2218, t(16) = 1.271) but increased the consumption of sucrose compared with control mice (n = 9 mice/group, Mann-Whitney test, p = 0.0400, U = 17) in the sucrose preference test (SPT). Data were shown as mean ± SEM. *p < 0.05, **p < 0.01; n.s., no significant difference. Source data are provided as a Source Data file.