Fig. 7: Convergent transcriptional patterns in NAc between Ctx withdrawal in rats and human CUD.

A Schematic posing the comparison between WD/Ext modalities in rats and human CUD. B RRHO2 plots reveal a robust and global transcriptional concordance between Ctx rats and CUD (left panels core/shell) and predominant discordant patterns when CUD is compared against HC or Ext groups (middle and right panels core/shell). Concordance/ Discordance; same or opposite direction of yellow /magenta arrows. C Union heatmaps showing a similar distribution of DEGs between CUD and Ctx groups, which is consistent with the RRHO2 results. Upregulation: yellow or downregulation: blue (nominal p < 0.05, ±25% fold-change; 1.25). D Venn diagrams showing the proportion of DEGs and their relationship (overlap) between CUD and WD/Ext conditions in NAc-subregions. Note that the CUD data were obtained from whole NAc encompassing both subregions (Mews and Cunningham et al.⁹). E Union heatmaps (upper panel) highlighting the shared genes and their expression direction (up = yellow, blue = down) between CUD and Ctx datasets, as well as the consequent upstream regulators for NAc-core. Activation z scores: Activated (yellow) = overrepresentation of targets activated by the regulator; Suppressed (blue) = overrepresentation of targets repressed by the regulator; black/gray = not a predicted upstream regulator. F Overlapping top gene ontology (GO) terms between CUD (whole NAc) and across WD/Ext conditions in NAc subregions with a notable enrichment of DEGs associated with cytokine, GTPase and plasma membrane signaling. Dot size is reflective of the number of genes per gene ontology term. Created in BioRender. Holt, L. (2025) https://BioRender.com/q81g274’ (MS27SN28G4).