Fig. 2: Raclopride, but not aripiprazole, induces neuronal activation in the VTA. | Translational Psychiatry

Fig. 2: Raclopride, but not aripiprazole, induces neuronal activation in the VTA.

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

Fig. 2

a, b Representative images showing Fos and D2R immunoreactivity in the Cpu, 105 min after administration of vehicle, ketamine, raclopride plus ketamine or aripiprazole plus ketamine (scale bar is 50 μm, allows indicate Fos/D2 double-positive cells), as well as the number of Fos/D2R-double-positive cells in the Cpu (vehicle: n = 7 slices from 2 mice; ketamine: n = 17 slices from 5 mice; raclopride plus ketamine: n = 22 slices from 5 mice; aripiprazole plus ketamine: n = 18 slices from 5 mice). Dunn’s multiple comparisons test, ***P < 0.001, ****P < 0.0001. c Quantification of Fos immunostaining in the various brain regions associated with antidepressant effects 105 min after administration of vehicle (gray, n = 10–46 slices from 4 mice), ketamine (red, n = 18–43 slices from 4 mice) or aripiprazole plus ketamine (green, n = 14–38 slices from 4 mice). Dunn’s multiple comparisons test or Dunnett’s multiple comparisons test was used depending on normality. **P < 0.01, ***P < 0.001, ****P < 0.0001. d Quantification of Fos immunostaining in multiple brain regions associated with antidepressant effects 105 min after administration of vehicle (gray, n = 22–42 slices from 4 mice), ketamine (red, n = 18–40 slices from 4 mice) or raclopride plus ketamine (blue, n = 19–46 slices from 4 mice). Dunn’s multiple comparisons test or Dunnett’s multiple comparisons test was used depending on normality. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. e Hierarchical clustering of mice and brain regions by Fos+ cell density. f Correlation matrix of Fos+ cell densities between pairs of brain regions. g Network consisting of the nodes of brain regions and connections of Pearson’s r with the absolute value > 0.5. The color scale shows eigenvector centrality. h D2R mRNA expression map in depression-related brain regions from Allen brain map dataset (https://portal.brain-map.org/). ACC anterior cingulate cortex, BLA basolateral amygdaloid nucleus, DR dorsal raphe nucleus, LHA lateral hypothalamus, LHb lateral habenula, mPFC medial prefrontal cortex, NAc nucleus accumbens, PAG periaqueductal gray, PTg pedunculotegmental nucleus, PVT paraventricular nucleus of the thalamus, RSC retrosplenial cortex, VP ventral pallidum, VTA ventral tegmental area.

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