A low-dose combination of ketamine 1 mg/kg (Ket-1) and lithium 10 mg/kg (Ket-1/Li-10) stimulates mammalian target of rapamycin (mTOR) signaling and inhibits the glycogen synthase kinase-3β (GSK-3β) in rat prefrontal cortex. Rats were administered saline, Ket-1, Li-10, or Ket-1/Li-10 and 1 h (a, b) or 24 h (c) later tissue was harvested for synaptosomal preparations. Levels of phosphorylated forms of mTOR, extracellular signal-regulated kinase (ERK), Akt, S6K, and GSK-3β were determined by western blot and were normalized to the levels of total protein. The results are expressed as fold change compared with saline control and are shown as the mean±SEM (n=5–8; *p<0.05, **p<0.01 compared with saline group; analysis of variance (ANOVA)).