Microarray analysis was performed on NAc of sham- and morphine-pelleted mice under control or VTA BDNF knockdown conditions. (A) Heatmap of up (red)- or down (green)-regulated NAc genes upon knockdown of VTA BDNF. (B) Heatmap of up- or down-regulated NAc genes by morphine regardless of knockdown of VTA BDNF. (C) Venn diagrams of genes that were uniquely regulated by morphine (red) or by knockdown of VTA BDNF (blue), and of genes that were regulated by morphine and knockdown of VTA BDNF in an interactive manner (green). (D to G) Alterations of sox11 (D and E) and gadd45g (F and G) expression in NAc from heatmap of microarray analysis (D and F) and qRT-PCR validation (E and G). One-way ANOVA for qRT-PCR validation, Fisher’s PLSD test, τp < 0.1, *p < 0.05, ***p < 0.001 compared to sham+AAV-GFP controls; $p < 0.1, #p < 0.05, ###p < 0.001 compared to sham+AAV-CreGFP mice, n = 9–12. (H) Reduction of sox11 expression using AAV-shRNA-Sox11 increases morphine CPP (10 mg/kg, sc). Fisher’s PLSD test, *p < 0.05 compared with AAV-GFP controls; #p < 0.05 compared with AAV-scrambled controls, n = 11–12. (I) Sox11 overexpression in NAc using HSV-Sox11 decreases morphine CPP (15 mg/kg, sc). t-test, *p < 0.05, n = 8. (J) Enhancement of morphine reward (15 mg/kg, sc) induced by knockdown of VTA TrkB is counteracted by sox11 overexpression in NAc. Fisher’s PLSD test, *p < 0.05 compared with HSV-tomato (TMT) (NAc)+AAV-GFP (VTA) controls; #p < 0.05 compared with HSV-TMT (NAc)+AAV-CreGFP (VTA) mice. (K) Enhancement of morphine reward (12.5 mg/kg, sc) induced by knockdown of VTA TrkB is further enhanced by gadd45g overexpression in NAc. Fisher’s PLSD test, *p < 0.05 compared to HSV-GFP+AAV-GFP controls; #p < 0.05, ###p < 0.001 compared to HSV-Gadd45g+AAV-CreGFP.