The major mode of signaling for both CRF receptors is coupling to Gsα and activating the adenylyl cyclase-protein kinase A cascade although CRF1 and CRF2 receptors can also signal via the phospholipase C-protein kinase C cascade in certain cells and neurons. Gs-coupled CRF1 receptor signaling is stringently regulated by GRK3- and βarrestin2-mediated homologous desensitization. CRF receptors can also activate Akt, NFκB, ERK, STAT, and Bax, which are potential molecular targets for PTSD possibly under regulation by βarrestin2 scaffolding and other upstream signaling proteins.