WGCNA identified several coordinately-expressed groups of genes (modules) that were treatment-responsive. Six modules in the amygdala and three in the PFC were responsive to both effective treatments (feno and tesa). The direction of change for the feno- and tesa-regulated genes is in the same direction for amygdala (but not for PFC), suggesting that the expression changes in amygdala are more crucial for mediating decreased ethanol consumption at the time point analyzed. In the amygdala, many of the differentially expressed (up-regulated) neuropeptide signaling genes were also coordinately regulated by feno and tesa, respectively, as follows: Avp (46%; 52%), Pdyn (23%; 24%), Penk1 (34%; 49%), Tac1 (49%; 48%), Tac2 (16%; 12%), Scg2 (47%; 29%), Gnas (7%; 6%), Npy (6%; 7%) and Pmch (8%; 7%). There were 14 other neuropeptide genes that were co-expressed in the same module, but not significantly regulated by feno and tesa. Neuropeptide signaling in the amygdala has established roles in stress/anxiety and alcohol drinking behavior. Pioglitazone and rosiglitazone (PPARγ agonists) demonstrated anti-depressant-like effects in rodents 1, 51 and rosiglitazone reduced physiological responses to psychological stress in rats 50.
