We identified 20 out of 35 modules that were treatment-responsive in the PFC with 4,853 out of 19,400 genes in the grey category. Three modules (green, tan and blue) were responsive to both working treatments (Table S11) and were enriched for genes that are up-regulated by feno and down-regulated by tesa. This is in contrast to the amygdala where the treatment-responsive modules were enriched for feno- and tesa-regulated genes with the same direction of fold change. Two of the three modules were enriched with neuronal genes. We found PPI networks related to glutamate signaling pathways in two of the three modules, and glutamate receptor activity ontologies were enriched in all three treatment-responsive modules. Families of genes that were enriched included those involved in synaptic transmission (e.g., Kcna1, Kcnd2, Kcnj12, Scn3a, Cacna2d1, Gabrb2, Itpr1, Trpc1), especially as it pertains to learning (long-term depression), mostly due to the coordinated regulation of many glutamate receptors (e.g., Grm7, Gria1, Gria3, Grid2, Grin1). One module (tan) was enriched with genes known to be important for alcohol consumption (Bdnf, Ccnd2, Gabrb2, Gnas, Grin2a and Grm5) with a hypergeometric p < 0.02.
