Fig. 3

Effects of TPPU on MWT and SPT scores and on the levels of sEH, AHR, and TSPO. A Schedule of the experiment. SNI surgery was performed after acclimation. TPPU (3 mg/kg, once daily) was administered orally for 7 consecutive days, starting at day 14 after SNI. 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 40 SNI mice were classified into anhedonia-susceptible and anhedonia-resilient groups via a hierarchical cluster analysis of the SPT results. C MWT [Time: F (9, 63) = 19.33, P < 0.001; Group: F (3, 21) = 173.5, P < 0.001; Interaction: F (27, 189) = 7.369, P < 0.001] was measured on days 7, 14, 15, 16, 17, 18, 19, 20 and 21 in the Sham + Veh, Sham + TPPU, Sus + Veh, and Sus + TPPU groups after SNI. ^***P < 0.001, Sham + Veh group vs. Sus + Veh group; ^###P < 0.001, Sus + Veh group vs. Sus + TPPU group. D SPT [Time: F (1, 56) = 10.34, P < 0.01; Group: F (3, 56) = 33.17, P < 0.001; Interaction: F (3, 56) = 8.744, P < 0.001] was performed in the Sham + Veh, Sham + TPPU, Sus + Veh, and Sus + TPPU groups on days 12 and 21 after SNI. ^**P < 0.01, ^***P < 0.001. E CYP1A1 level in the serum [TPPU: F (1, 20) = 10.73, P < 0.01; Group: F (1, 20) = 8.407, P < 0.01; Interaction: F (1, 20) = 22.69, P < 0.001]. F CYP1B1 level in the serum [TPPU: F (1, 20) = 1.241, P = 0.28; Group: F (1, 20) = 0.06, P = 0.8; Interaction: F (1, 20) = 0.436, P = 0.52]. G IL-1β level in the serum [TPPU: F (1, 20) = 8.976, P < 0.01; Group: F (1, 20) = 4.557, P < 0.05; Interaction: F (1, 20) = 11.16, P < 0.01]. (H) TNF-α level in the serum [TPPU: F (1, 20) = 55.45, P < 0.001; Group: F (1, 20) = 88.65, P < 0.001; Interaction: F (1, 20) = 55.45, P < 0.001]. I Effects of TPPU on sEH expression. mPFC [TPPU: F (1, 28) = 0.1376, P = 0.71; Group: F (1, 28) = 1.615, P = 0.21; Interaction: F (1, 28) = 0.2046, P = 0.65]; hippocampus [TPPU: F (1, 28) = 18.62, P < 0.001; Group: F (1, 28) = 3.055, P = 0.09; Interaction: F (1, 28) = 15.77, P < 0.001]; spinal cord [TPPU: F (1, 28) = 11.33, P < 0.001; Group: F (1, 28) = 0.1966, P = 0.67; Interaction: F (1, 28) = 15.28, P < 0.001]; liver [TPPU: F (1, 28) = 44.43, P < 0.001; Group: F (1, 28) = 2.362, P = 0.14; Interaction: F (1, 28) = 10.38, P < 0.01]; kidney [TPPU: F (1, 28) = 51.25, P < 0.001; Group: F (1, 28) = 1.287, P = 0.26; Interaction: F (1, 28) = 9.837, P < 0.01]; gut [TPPU: F (1, 28) = 18.49, P < 0.001; Group: F (1, 28) = 3.879, P = 0.06; Interaction: F (1, 28) = 15.33, P < 0.001]. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. J Effects of TPPU on AHR expression. mPFC [TPPU: F (1, 28) = 0.0119, P = 0.91; Group: F (1, 28) = 0.016, P = 0.9; Interaction: F (1, 28) = 0.1949, P = 0.66]; hippocampus [TPPU: F (1, 28) = 18.04, P < 0.001; Group: F (1, 28) = 1.015, P = 0.32; Interaction: F (1, 28) = 10.42, P < 0.01]; spinal cord [TPPU: F (1, 28) = 0.6641, P = 0.42; Group: F (1, 28) = 1.8, P = 0.19; Interaction: F (1, 28) = 2.695, P = 0.11]; liver [TPPU: F (1, 28) = 10.73, P < 0.01; Group: F (1, 28) = 44.97, P < 0.001; Interaction: F (1, 28) = 8.917, P < 0.01]; kidney [TPPU: F (1, 28) = 39.57, P < 0.001; Group: F (1, 28) = 5.957, P < 0.05; Interaction: F (1, 28) = 21.38, P < 0.001]; gut [TPPU: F (1, 28) = 5.764, P < 0.05; Group: F (1, 28) = 59.08, P < 0.001; Interaction: F (1, 28) = 6.479, P < 0.05]. Data are reported as the mean ± SEM (n = 8). ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. K Effects of TPPU on TSPO expression. mPFC [TPPU: F (1, 28) = 0.0844, P = 0.77; Group: F (1, 28) = 0.0057, P = 0.94; Interaction: F (1, 28) = 0.4106, P = 0.53]; hippocampus [TPPU: F (1, 28) = 6.114, P < 0.05; Group: F (1, 28) = 9.662, P < 0.01; Interaction: F (1, 28) = 2.828, P = 0.1]; spinal cord [TPPU: F (1, 28) = 6.981, P < 0.05; Group: F (1, 28) = 3.933, P = 0.06; Interaction: F (1, 28) = 7.76, P < 0.01]; liver [TPPU: F (1, 28) = 0.7191, P = 0.4; Group: F (1, 28) = 0.015, P = 0.9; Interaction: F (1, 28) = 0.6986, P = 0.41]; kidney [TPPU: F (1, 28) = 6.278, P < 0.05; Group: F (1, 28) = 14.19, P < 0.001; Interaction: F (1, 28) = 6.607, P < 0.05]; gut [TPPU: F (1, 28) = 0.3, P = 0.86; Group: F (1, 28) = 0.3095, P = 0.58; Interaction: F (1, 28) = 0.9039, P = 0.34]. Data are reported as the mean ± SEM (n = 8). ^*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, 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, Veh vehicle