Fig. 2: Ketamine changes circadian clock gene expression in the mouse mPFC and opposes CDM effects.

a Schematic overview of the CDM paradigm, saline/ 3 mg/kg ketamine (KET) administration at ZT00 (start of the resting phase); tissue harvesting time points and gene expression analyses. b Relative mRNA expression of clock genes Per1, Per2, Cry1, Cry2, Bmal1, Rorα, Rev-erbα, Rorβ normalized to s12, ApoE, and GAPDH in mPFC samples from CDM mice injected at ZT00 with saline (CDM) or ketamine (KET) and harvested every 4 h from ZT06 (6 h after injection) till ZT06 (30 h post injection) (n = 5 mice per group, two-way ANOVA: P values of the CDM effect is displayed inside the graph, Bonferroni post hoc test: *P < 0.05, **P < 0.01, ***P < 0.001 CDM vs. KET). c Relative mRNA expression of clock genes Per1, Per2, Cry1, Cry2, Bmal1, Rorα, Rev-erbα, Rorβ normalized to s12, ApoE and GAPDH in mPFC samples from naive mice injected at ZT00 with saline (control) and ketamine (KET) and harvested at ZT06 (6 h after injection), ZT18 (18 h after injection) and ZT06 (30 h post injection) (n = 5 mice per group, two-way ANOVA with Bonferroni post hoc test: *P < 0.05, **P < 0.01, ***P < 0.001 control vs. KET). d Schema summarizing the effects of ketamine on clock gene expression in mPFC – ketamine downregulates Per and Cry clock suppressors and increases Rorα. Data are presented as mean ± SEM. See also Supplementary Fig. 2 and Supplementary Data 1. Source data are provided as a Source Data file.