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. 2024 Aug 23;15:7257. doi: 10.1038/s41467-024-51716-9

Fig. 6. Pharmacological activation of RORα/γ elicits rapid antidepressant effects dependent on Bmal1 and Homer1a in mPFC.

Fig. 6

a Experimental design: baseline behavioral assessment in IntelliCage, followed by CDM paradigm and test phase 24 h after i.p. injection of vehicle/RORα/γ agonist SR1078 (10 mg/kg). b Sucrose preference assessed in IntelliCage at baseline and 24 h post vehicle/SR10067 i.p. injection (at ZT06) (n = 9 mice, repeated measures two-way ANOVA with Bonferroni post hoc test: **P < 0.01, ***P < 0.001). c Immobility time during test phase FST (n = 14 mice, two-tailed Student’s t test: ***P < 0.0001). d Immobility time during test phase TST (n = 14 mice, two-tailed Student’s t test: *P = 0.0003). e Relative mRNA expression of Bmal1 and Homer1a at ZT06 in mPFC 24 h post vehicle/SR1078 injection (n = 5 mice, two-tailed Student’s t test: *P < 0.05). f Experimental strategy: AAV-induced mPFC CaMK2a-Bmal1KO, followed after 3 weeks by CDM paradigm; acute i.p. injection of vehicle/SR1078 (10 mg/kg) followed 24 h later by test phase. g Immobility time of test phase FST (left) and TST (right) (n = 7 mice, two-tailed Student’s t test). h Relative mRNA expression of Homer1a at ZT06 in mPFC 24 h post vehicle/SR1078 injection of mPFC CaMK2a-Bmal1KO mice (n = 4 mice, two-tailed Student’s t test). i Experimental strategy of Homer1a KD: CDM protocol on WT mice before bilateral stereotactic injection of Accell siCntr/siHomer1a; followed by i.p. injection of vehicle/SR1078 (10 mg/kg) and test phase after 24 h. j Relative mRNA expression of Homer1a in mPFC of siCntr (n = 6) and siHomer1a (n = 7) injected mice (two-tailed Student’s t test: ***P < 0.001). k Immobility time during test phase FST (left) and TST (right) in siCntr/siHomer1a animals after administration of vehicle/SR1078 (n = 7 mice, two-way ANOVA with Bonferroni post hoc test: *P < 0.05). Data are presented as mean ± SEM and the individual data points are depicted. See also Supplementary Fig. 6 and Supplementary Data 1. Source data are provided as a Source Data file.