Supplementary Table 1 The tables show the measures of anxiety-like behavior by home-cage emergence (1a) and open-field (1b) tests, food motivation by food.

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Supplementary Table 1 The tables show the measures of anxiety-like behavior by home-cage emergence (1a) and open-field (1b) tests, food motivation by food intake test (1c), levels of anhedonia by sucrose intake test (1d), and forced swim immobility behavior (1e) in the naïve animal experiments. The behavioral data were analyzed using two-tailed Student t-test, in comparison from each deep brain stimulation (DBS) group to their respective sham implanted animals. Note. LFS of the LHb, and HFS of the vmPFC, NAc core, and LHb reduced the escape latency from the home-cage emergence test, indicating anxiolytic behavior. In food intake test, HFS of the vmPFC, NAc core and VTA increased motivation for food consumption. For hedonia measure, HFS of the vmPFC and VTA increased sucrose intake levels. In behavioral despair, HFS of the vmPFC and NAc core reduced forced swim immobility behavior. Data represent mean ± S.E.M. Indication: *, significant difference from the respective sham implanted animals, (p<0.05).

Home-cage Emergence Test (Escape Latency, s) GroupsDBSShamEffects Cg LFS ± 0 * ± t(10)=2.453, p=0.034 HFS ± 50.06t(10)=-1.895, p=n.s. vmPFC LFS ± ± t(12)=1.690, p=n.s. HFS ± * t(12)=-2.226, p=0.046 NAc (core) LFS ± ± t(9)=-0.562, p=n.s. HFS ± * t(7)=-4.906, p=0.002 NAc (shell) LFS ± ± 0 t(9)=-1.367, p=n.s. HFS ± t(8)=-1.340, p=n.s. LHb LFS ± * ± 0 t(7)=-6.507, p<0.001 HFS ± * t(9)=-8.192, p<0.001 VTA LFS ± ± 0 t(8)=-1.398, p=n.s. HFS ± 76.64t(9)=-1.512, p=n.s. 1(a)

1(b) Open-Field Test (Center zone, s) GroupsDBSShamEffects Cg LFS 8.00 ± 1.91 * ± 7.38 t(9)=-2.453, p=0.044 HFS25.18 ± 3.58t(9)=0.682, p=n.s. vmPFC LFS 5.15 ± 1.05 * ± 7.06 t(9)=-3.011, p=0.015 HFS24.93 ± 3.27t(10)=0.997, p=n.s. NAc (core) LFS14.40 ± ± 5.76 t(9)=-0.853, p=n.s. HFS29.51 ± 6.51t(8)=1.000, p=n.s. NAc (shell) LFS27.97 ± ± 6.50 t(6)=1.379, p=n.s. HFS12.69 ± 1.27t(7)=1.065, p=n.s. LHb LFS28.53 ± ± 6.80 t(6)=1.518, p=n.s. HFS18.93 ± 2.44t(6)=0.462, p=n.s. VTA LFS20.20 ± ± 4.40 t(6)=0.852, p=n.s. HFS19.46 ± 2.70t(9)=1.113, p=n.s.

1(c) Food Intake Test (g) GroupsDBSShamEffects Cg LFS6.08 ± ± 0.59 t(10)=-1.635, p=n.s. HFS9.39 ± 0.55t(10)=1.169, p=n.s. vmPFC LFS8.19 ± ± 0.79 t(12)=1.654, p=n.s. HFS ± 0.21 * t(12)=8.320, p<0.001 NAc (core) LFS5.78 ± ± 0.55 t(10)=-1.450, p=n.s. HFS ± 0.37 * t(10)=4.707, p=0.001 NAc (shell) LFS9.61 ± ± 1.24 t(9)=2.154, p=n.s. HFS8.37 ± 0.87t(9)=1.015, p=n.s. LHb LFS8.94 ± ± 0.33 t(9)=0.582, p=n.s. HFS9.47 ± 0.47t(9)=1.438, p=n.s. VTA LFS8.78 ± ± 0.87 t(8)=1.898, p=n.s. HFS 9.24 ± 0.68 * t(8)=2.505, p=0.037

1(d) Sucrose Intake Test (g/kg) GroupsDBSShamEffects Cg LFS10.98 ± ± 1.33 t(10)=-1.216, p=n.s. HFS13.23 ± 2.24t(10)=1.884, p=n.s. vmPFC LFS12.11 ± ± 1.09 t(9)=2.194, p=n.s. HFS ± 2.55 * t(8)=2.818, p=0.023 NAc (core) LFS8.48 ± ± 4.56 t(9)=-0.078, p=n.s. HFS16.63 ± 2.96t(8)=1.457, p=n.s. NAc (shell) LFS7.63 ± ± 3.67 t(9)=-0.494, p=n.s. HFS12.28 ± 2.92t(10)=0.484, p=n.s. LHb LFS6.43 ± ± 3.72 t(9)=-1.054, p=n.s. HFS15.89 ± 2.96t(8)=1.234, p=n.s. VTA LFS10.71 ± ± 0.87 t(8)=-0.177, p=n.s. HFS ± 1.83 * t(8)=2.505, p=0.037

1(e) Forced Swim Immobility (duration, s) GroupsDBSShamEffects Cg LFS288.0 ± ± t(7)=0.179, p=n.s. HFS334.0 ± 38.03t(7)=1.037, p=n.s. vmPFC LFS353.50± ± t(8)=-0.765, p=n.s. HFS ± * t(8)=-2.513, p=0.036 NAc (core) LFS ± ± t(7)=0.073, p=n.s. HFS ± * t(7)=-3.031, p=0.019 NAc (shell) LFS ± ± t(9)=-1.097, p=n.s. HFS ± 25.57t(8)=-1.520, p=n.s. LHb LFS ± ± t(7)=-1.480, p=n.s. HFS ± 32.42t(7)=-2.130, p=n.s. VTA LFS ± ± t(9)=-0.483, p=n.s. HFS ± 34.79t(9)=-1.339, p=n.s.

Supplementary Table 2 The tables show the measures of anxiety-like behavior by home-cage emergence (2a) and open-field (2b) tests, food motivation by food intake test (2c), levels of anhedonia by sucrose intake test (2d), and forced swim immobility behavior (2e) in the chronic unpredictable stress (CUS) rat model of depression. The behavioral data were analyzed using one-way ANOVA with Bonferroni post-hoc tests for multiple comparisons from each deep brain stimulation (DBS) group to their respective sham implanted animals and non-CUS control group. Note. HFS of the vmPFC and NAc core reduced the escape latency from the home-cage emergence test, indicating anxiolytic behavior. However, HFS of the vmPFC, but not other DBS targets, increased hedonia level in the sucrose intake test, and time spent in the center zone of the open- field test. For behavioral despair measure, HFS of the vmPFC and LHb reduced forced swim immobility behavior as compared to the respective CUS sham implanted animals. Data represent mean ± S.E.M. Indication: *, significant difference from the respective CUS implanted sham animals; #, significant difference from the non-CUS control group, (p<0.05).

Home-cage Emergence Test (Escape Latency, s) GroupsDBS (CUS)Sham (CUS)ControlEffects vmPFC ± * ± 0 # ± F (2, 20) =23.664, p<0.001 NAc (core) ± * ± # F (2, 21) =7.927, p=0.003 NAc (shell) ± # ± F (2, 20) =5.636, p=0.013 LHb ± ± # F (2, 23) =6.251, p= (a) 2(b) Open-Field Test (Center zone, s) GroupsDBS (CUS)Sham (CUS)ControlEffects vmPFC ± 3.86 * 7.58 ± 1.28 # ± 2.93 F (2, 19) =5.346, p= NAc (core) ± 2.35 # ± 9.07F (2, 22) =4.340, p=0.026 NAc (shell) ± 2.36 # ± 4.60 # F (2, 19) =7.088, p=0.005 LHb ± 2.75 # ± 6.70F (2, 22) =5.058, p=0.016

2(c) 2(d) Sucrose Intake Test (g/kg) GroupsDBS (CUS)Sham (CUS)ControlEffects vmPFC ± 2.82 * # 2.57 ± ± 2.00 F (2, 19) =8.216, p=0.003 NAc (core)4.95 ± ± 0.64F (2, 23) =0.853, p=n.s. NAc (shell) 1.56 ± 0.35 # 1.47 ± 0.54 # F (2, 19) =7.416, p=0.004 LHb9.05 ± ± 1.40F (2, 20) =0.647, p=n.s. Food Intake Test (g) GroupsDBS (CUS)Sham (CUS)ControlEffects vmPFC9.34 ± ± ± 0.46 F (2, 19) =1.136, p=n.s. NAc (core)7.12 ± ± 1.18F (2, 21) =1.876, p=n.s. NAc (shell)7.53 ± ± 1.12F (2, 18) =0.658, p=n.s. LHb7.18 ± ± 1.70F (2, 21) =1.431, p=n.s.

2(e) Forced Swim Immobility (duration, s) GroupsDBS (CUS)Sham (CUS)ControlEffects vmPFC ± 9.59 * ± # ± 7.74 F (2, 25) =12.052, p<0.001 NAc (core) ± # ± 17.48F (2, 23) =10.623, p=0.001 NAc (shell) ± # ± # F (2, 21) =24.531, p<0.001 LHb ± 9.95 * ± # F (2, 25) =22.287, p<0.001