Extended Data Fig. 3: Adenosine receptor activity is critical for ketamine’s antidepressant effects without altering locomotion or adenosine release.
From: Adenosine signalling drives antidepressant actions of ketamine and ECT
a, Total distance traveled in the open-field test for WT, A1 KO and A2A KO mice. b, c, Time-course (b) and quantification (c) of locomotor activity in WT, A1 KO and A2A KO mice following ketamine (10 mg·kg−1, i.p.) and saline administration. Mouse sample sizes (n) are shown in b. d, Time course of extracellular adenosine levels in the mPFC of WT, A1 KO and A2A KO mice after equal dose of ketamine, quantification of area under the curve (AUC, normalized to WT). e, Experimental timeline for assessing the impact of adenosine receptor antagonists on the antidepressant effects of ketamine. f-i. Effects of pretreatment with adenosine receptor antagonists (PSB36 for A1 and ZM241385 for A2A; 1 mg·kg−1, i.p.) on ketamine’s antidepressant actions (forced swimming immobility: f, h; sucrose preference: g, i) 1 h (f, g) and 24 h (h, i) after ketamine administration. j, upper, Experimental timeline for testing the effect of adenosine receptor antagonists on the antidepressant-like action of ketamine in a lipopolysaccharide (LPS)-induced depression model. lower, Effects of pretreating an A1 antagonist (PSB36, 1 mg·kg−1, i.p.) and A2A antagonist (ZM241385, 1 mg·kg−1, i.p.) on ketamine’s antidepressant actions in a FST test of LPS-challenged mice. Data are mean ± s.e.m. (error bars in a–c, f-j; shading in d). Two-tailed unpaired t-tests were used for a, c, d, f-j (*P < 0.05, **P < 0.01, ***P < 0.001). See Supplementary Table 1 for detailed statistics. The schematics in e and j were created using BioRender (https://www.biorender.com).
