Fig. 4

An AHR agonist attenuated the antidepressant effects, but not the analgesic effects of TPPU. A Schedule of the experiment. SNI surgery was performed after acclimation. CH-223191 (10 mg/kg, once daily) and TPPU (3 mg/kg, once daily) were administered orally for 7 consecutive days, starting at 14 after SNI. FICZ (100 µg/mg) was administered orally on day 14. MWT was measured on days 7, 14, 15, 16, 17, 18, 19, 20, and 21 after SNI. The SPT was performed on days 5, 12, and 21 after SNI. B Dendrogram of the hierarchical clustering analysis. A total of 33 SNI mice were classified into anhedonia-susceptible and anhedonia-resilient groups based on SPT scores. C MWT [Time: F (9, 45) = 61.2, P < 0.001; Group: F (4, 20) = 128.8, P < 0.001; Interaction: F (36, 180) = 8.887, P < 0.001] was measured on days 7, 14, 15, 16, 17, 18, 19, 20, and 21 after SNI in the Sham, Sus, Sus + CH-223191, Sus + FICZ, and Sus + FICZ + TPPU groups. ^***P < 0.001, Sus group vs. Sus + FICZ + TPPU group; ^###P < 0.001, Sus + FICZ group vs. Sus + FICZ + TPPU group. D The SPT [F(4, 25) = 10.86, P < 0.001] was performed in the sham, Sus, Sus + CH-223191, Sus + FICZ, and Sus + FICZ + TPPU groups on day 21 after SNI. *P < 0.05, **P < 0.01. E CYP1A1 level in the serum [F (4, 25) = 6.211, P < 0.01].F CYP1B1 level in the serum [F (4, 25) = 1.964, P = 0.13]. G IL-1β level in the serum [F (4, 25) = 15.85, P < 0.01]. H TNF-α level in the serum [F (4, 25) = 4.449, P < 0.01]. I Effects of TPPU on sEH expression. mPFC [F (4, 25) = 8.255, P < 0.001]; hippocampus [F (4, 25) = 21.93, P < 0.001]; spinal cord [F (4, 25) = 7.137, P < 0.001]; liver [F (4, 25) = 3.81, P < 0.05]; kidney [F (4, 25) = 7.236, P < 0.001]; gut [F (4, 25) = 12.33, P < 0.001]. *P < 0.05, **P < 0.01, ***P < 0.001. J Effects of TPPU on AHR expression. mPFC [F (4, 25) = 5.272, P < 0.01]; hippocampus [F (4, 25) = 48.4, P < 0.001]; spinal cord [F (4, 25) = 0.2683, P = 0.90]; liver [F (4, 25) = 18.69, P < 0.001]; kidney [F (4, 25) = 41.8, P < 0.001]; gut [F (4, 25) = 5.395, P < 0.01]. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. K Effects of TPPU on TSPO expression. mPFC [F (4, 25) = 0.9551, P = 0.45]; hippocampus [F (4, 25) = 8.753, P < 0.001]; spinal cord [F (4, 25) = 6.161, P < 0.01]; liver [F (4, 25) = 0.3481, P = 0.84]; kidney [F (4, 25) = 2.627, P = 0.059]; gut [F (4, 25) = 0.9321, P = 0.46]. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. AHR aryl hydrocarbon receptor, CYP1A1 cytochrome P450, family 1, subfamily A, polypeptide 1, CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1, FICZ 6-formylindolo[3,2-b]carbazole, sEH soluble epoxide hydrolase, mPFC medial prefrontal cortex, NS not significant, SNI spared nerve injury, Sus susceptible, TPPU 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, TSPO translocator protein