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. 2019 May 20;129(6):2542–2554. doi: 10.1172/JCI126859

Figure 5. BDNF is required for antidepressant actions of NV-5138.

Figure 5

(A–E) The antidepressant actions of NV-5138 are blocked by infusion of BDNF nAb into the mPFC. (A) BDNF nAb or control IgG (0.5 μg/side) was infused into the mPFC 30 minutes prior to administration of vehicle or NV-5138 (160 mg/kg, p.o.). (B and D) NV-5138 significantly decreased immobility time (B) in the FST (effect of NV-5138: F1,29 = 14.6, P < 0.001; mPFC infusion: F1,29 = 13.4, P < 0.001; interaction: F1,29 = 14.9, P < 0.001) and latency to feed (D) in the NSFT (effect of NV-5138: F1,29 = 39.4, P < 0.001; mPFC infusion: F1,29 = 11.2, P = 0.002; interaction: F1,29 = 18.0, P < 0.001), and these effects were blocked by infusion of the BDNF nAb. (C and E) There were no significant effects on locomotor activity (effect of NV-5138: F1,30 = 0.01, P = 0.92; mPFC infusion: F1,30 = 0.07, P = 0.79; interaction: F1,30 = 0.03, P = 0.86) or HCF (effect of NV-5138: F1,30 = 0.11, P = 0.74; mPFC infusion: F1,30 = 2.93, P = 0.1; interaction: F1,30 = 1.23, P = 0.28). (F–J) The antidepressant actions of NV-5138 are attenuated in BDNF Val66Met knockin mice. (F) Experimental time line for behavioral testing of animals after vehicle or NV-5138 administration. In the BDNF Val/Val mice, NV-5138 treatment significantly decreased immobility time (G) in the FST (effect of NV-5138: F1,64 = 12.7, P < 0.001; genotype: F2,64 = 1.88, P = 0.16; interaction: F2,64 = 3.98, P = 0.02) and latency to feed (I) in the NSFT (effect of NV-5138: F1,65 = 13, P < 0.001; genotype: F2,65 = 12.8, P < 0.001; interaction: F2,65 = 3.4, P = 0.04) that were blocked in Val/Met and Met/Met mice. No significant effects were observed in (H) LMA (effect of NV-5138: F1,64 = 3.39, P > 0.05; genotype: F2,64 = 0.59, P = 0.56; interaction: F2,64 = 0.06, P = 0.94) or (J) HCF (effect of NV-5138: F1,65 = 0.065, P = 0.80; genotype: F2,65 = 0.52, P = 0.60; interaction: F2,65 = 0.58, P = 0.56). Results are shown as mean ± SEM. n = 7–9/group (A–E); n = 5–16/group (F–J). *P < 0.05; **P < 0.01; ***P < 0.001 (A–J), 2-way ANOVA and Tukey’s post hoc test.