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. 2023 Apr 5;14:1880. doi: 10.1038/s41467-023-37601-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — a Schematic protocol for investigating the role of the A_2AR antagonist KW6002 to reverse the CRS-induced depressive phenotypes. Hematoxylin and eosin (HE) staining showing the position of the cannulas. Scale bar: 1000 μm. b–d After confirming that the mice subject CRS displayed a depressive-like behaviors in the tail suspension test (TST) (n = 24 mice/group, Unpaired t test, p = 0.0476, t(46) = 2.035) b and in the open field test (OFT) (c: n = 24 mice/group, Unpaired t test, p = 0.0006, t(46) = 3.671; d: n = 24 mice/group, Mann–Whitney test, p = 0.5295, U = 257), e–g injection of KW6002 (0.5 µg/µL, 2 µL) into the LS for three consecutive days reversed the increased immobility in the TST caused by CRS (n = 13 (Vehicle: no-stress), 11 (Vehicle: CRS), 11 (KW6002: no-stress) or 10 (KW6002: CRS) mice/group, one-way ANOVA, interaction p = 0.0269, F(1,41) = 5.268; p(Vehicle: no-stress vs. Vehicle: CRS) = 0.0000071, q(41) = 8.037; p(Vehicle: no-stress vs. KW6002: no-stress) = 0.0500, q(41) = 3.787; p(Vehicle: CRS vs. KW6002: CRS) = 0.0000077, q(41) = 8.000; p(KW6002: no-stress vs. KW6002: CRS) = 0.1453, q(41) = 3.086) e, but did not affect the performance of mice in the OFT (n = 13, 11, 11 and 10 samples per group, respectively, one-way ANOVA, interaction p = 0.4239, F(1,41)=0.6524; p(Vehicle: no-stress vs. Vehicle: CRS) = 0.9736, t(41)=0.7555; p(Vehicle: no-stress vs. KW6002: no-stress)=0.9968, t(41) = 0.5051; p(Vehicle: CRS vs. KW6002: CRS) = 0.5406, t(41) = 1.581; p(KW6002: no-stress vs. KW6002: CRS) = 0.9991, t(41) = 0.3989) (f) (n = 13, 11, 11 and 10 samples per group, respectively, one-way ANOVA, interaction p = 0.7041, F(1,41) = 0.1463; p(Vehicle: no-stress vs. Vehicle: CRS) = 0.0674, q(41) = 3.602; p(Vehicle: no-stress vs. KW6002: no-stress) = 0.9034, q(41)=0.9643; p(Vehicle: CRS vs. KW6002: CRS) = 0.9994, q(41) = 0.1627; p(KW6002: no-stress vs. KW6002: CRS) = 0.2594, q(41) = 2.636) (g). Data were shown as mean ± SEM. *p < 0.05, ***p < 0.001, ****p < 0.0001; n.s., no significant difference. Source data are provided as a Source Data file.