Systemic rapamycin (Rapa) resisted the elevation of mammalian target of Rapa (mTOR) signaling activity in the prefrontal cortex (PFC). After the rats were exposed to predictable chronic mild stress (PCMS), drug administration, and the behavioral tests, the levels of total and phosphorylated (p) mTOR and S6 ribosomal protein (rpS6) in the PFC, hippocampus, and amygdala were determined by western blot. Rapa blocked the elevation of p-mTOR and p-rpS6 levels in the PFC compared with the control groups (a, c) and did not change p-mTOR or p-rpS6 levels in the hippocampus (Hip) (e, g) or amygdala (Amy) (i, k). Total mTOR and rpS6 levels were not significantly changed in the PFC (b, d), Hip (f, h), or Amy (j, l) in the four groups. The data are expressed as mean±SEM. Representative band intensities of the western blot are shown on the bottom (n=6 per group). *p<0.05, compared with the control group; #p<0.05, PCMS-Rapa group compared with PCMS-vehicle (Veh) group.