In the PFC, CMS ↓Akt and PI3K mRNA expression. Desipramine and duloxetine ↑ CMS-induced Akt levels, but only desipramine restored PI3K levels. CMS ↓Nrf2 mRNA and protein expression levels. Nrf2 inhibitors Keap-1 and p-GSK-3β/GSK-3β ratio ↑ after CMS. Desipramine and duloxetine to CMS rats restored the expression of Nrf2, returned Keap-1 to Ctrl levels and showed a trend towards returning the p-GSK-3b/GSK-3b ratio to its Ctrl levels. CMS ↓ NQO-1, GPx1.AD treatment restored GPx1 levels. Desipramine ↑HO-1. PAR g is modulated by the AD treatments in the PFC. Here, AKT1 is linked to Alzheimer disease.