Fig. 3: Intra-VTA infusion of raclopride attenuates the antidepressant effect of ketamine, and aripiprazole plus ketamine ameliorates social deficits in the SDS mouse model without activating VTA TH-positive neurons. | Translational Psychiatry

Fig. 3: Intra-VTA infusion of raclopride attenuates the antidepressant effect of ketamine, and aripiprazole plus ketamine ameliorates social deficits in the SDS mouse model without activating VTA TH-positive neurons.

From: Fine-tuning of dopamine receptor signaling with aripiprazole counteracts ketamine’s dissociative action, but not its antidepressant effect

Fig. 3

a Experimental procedures for social defeat stress (SDS), intra-VTA infusion and the social interaction test (SIT). b Representative behavioral traces 1 day after intra-VTA infusion of aCSF plus saline i.p., intra-VTA aCSF plus ketamine i.p. or intra-VTA raclopride plus ketamine i.p. in the SIT. c SI ratio in the SIT (aCSF + Sal: n = 7 mice; sCSF + Ket: n = 7 mice; Rac + Ket: n = 11 mice; mean ± s.e.m.; two-way repeated-measures ANOVA followed by Fisher’s LSD test, *P < 0.05). d Representative immunoreactivities for TH and Fos in the VTA of mice administered intra-VTA aCSF and saline i.p., intra-VTA aCSF and ketamine i.p., or intra-VTA raclopride and ketamine i.p., (scale bar is 50μm, allows indicate Fos/TH double-positive cells). e Quantitation of TH/Fos-double-positive cells in the VTA (aCSF + Sal: n = 7 slices from 3 mice; aCSF + Ket: n = 5 slices from 3 mice; Rac + Ket: n = 10 slices from 3 mice; Dunn’s multiple comparisons test, **P < 0.01). f, g Representative images of Fos and TH immunoreactivities in the VTA 105 min after the indicated i.p. treatments (scale bar is 50 μm, allows indicate Fos/TH double-positive cells), and the number of Fos/TH-double-positive cells (vehicle: n = 38 slices from 6 mice; ketamine: n = 35 slices from 6 mice; raclopride plus ketamine: n = 25 slices from 4 mice; aripiprazole plus ketamine: n = 24 slices from 4 mice; brexpiprazole plus ketamine: n = 14 slices from 3 mice; Dunn’s multiple comparisons test, **P < 0.01, ***P < 0.001). h Representative behavioral traces in the SIT, 1 day after i.p. administration of the indicated drugs. i Social interaction ratio in the SIT (vehicle: n = 47 mice; ketamine: n = 51 mice; aripiprazole plus ketamine: n = 18 mice; raclopride plus ketamine: n = 19 mice; brexpiprazole plus ketamine: n = 18 mice; two-way repeated-measures ANOVA followed by Dunnett’s multiple comparisons test, *P < 0.05, ***P < 0.001).

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