Figure 4:

Schematic including the DEGs within the orexin receptor pathway, GPCR signaling, and Tyrosine receptor Kinase (Trk) signaling enriched using ToppFunn, Gene Ontology (GO), Reactome enrichment analyses respectively. Receptors and gene products from the hit list for each pathway are included in this depiction. Solid arrows indicate direct regulation while dashed arrows indicate indirect regulation. Genes are colored to represent significant up regulation in green and down regulation in red. Additional pathway related genes that are included are colored blue. Within this diagram we see themes of synaptic plasticity in the pathways leading to actin/microtubule organization, neurite outgrowth, and GPC receptor recycling. We also see transcriptional plasticity, which is important response in addiction through the differential expression and regulation of activity regulated TFs (BDNF, ARC, DUSP2/4/6, ETV5, EGR1/2/5), chromatin remodelers (KAT6A, SUDS3, KCTD21). Together this diagram represents potential mechanisms by which these signaling pathways may be affected by opioid overdose.