Extended Data Fig. 2: Effect of ketamine metabolites and metabolism inhibitors on adenosine release in the mPFC.
From: Adenosine signalling drives antidepressant actions of ketamine and ECT
a, Schematic of ketamine metabolism pathways. b, c, Time course of extracellular adenosine levels in the mPFC (b) and and corresponding AUC (c) following administration of ketamine, norketamine (NK), (2 R,6 R)-HNK (all at 10 mg·kg−1, i.p.), or saline. Area under the curve (AUC, normalized to saline) (c) was calculated post-administration. d, e, Effect of ritonavir pretreatment (50 mg·kg−1, i.p.) on ketamine-induced adenosine release. d, Adenosine time course with and without ritonavir. e, Quantification of adenosine peak (ΔF/F %), time to peak, and AUC (normalized to vehicle). Recordings were performed on separate days in the same cohort of mice. f, g, Effect of ketoconazole pretreatment (50 mg·kg−1, i.p.) on ketamine-induced adenosine signals. Same conventions as in (d, e). h, i, Effects of ticlopidine pretreatment (20 mg·kg−1, i.p.) on ketamine-induced adenosine signals, displayed as in d, e. j-l, Time course and AUC of extracellular adenosine in the mPFC after administration of ritonavir (j), ketoconazole (k), or ticlopidine (l) alone, compared to vehicle. Data are mean ± s.e.m. (shading in b, d, f, h, j-l; error bars in c, j-l). Statistical analyses used a two-tailed paired t-test (e, g, i) and two-tailed unpaired t-tests (c, j-l) (**P < 0.01, ***P < 0.001). See Supplementary Table 1 for detailed statistics.
