Involvement of PKA, CaMKII, PKC, MAPK/ERK and PI3K in the acute antidepressant-like effect of ferulic acid in the tail suspension test

Ferulic acid (FA, 4-hydroxy-3-methoxycinnamic acid) is a phytochemical compound naturally present in several plants and foods that is approved as an antioxidant additive and food preservative. It exerts a beneficial action in chronic mild stress-induced depressive-like behavior and produces an acute antidepressant-like effect in the tail suspension test (TST) through the activation of the serotonergic system. This study was aimed at investigating the possible involvement of signaling pathways in the antidepressant-like effect of acute and oral administration of FA, in the TST in mice. The anti-immobility effect of orally administered FA (0.01 mg/kg, p.o.) was prevented by pretreatment of mice with H-89 (1 μg/site, i.c.v., an inhibitor of PKA), KN-62 (1 μg/site, i.c.v., an inhibitor of CaMKII), GF109203X (5 ng/site, i.c.v., an inhibitor of PKC), U0126 (5 μg/site, i.c.v., an inhibitor of MAPK/ERK) or LY294002 (10 nmol/site, i.c.v., an inhibitor of PI3K), all involved with neurotrophic signaling pathways. The results demonstrated that FA exerts antidepressant-like effect in the TST in mice, through the activation of signaling pathways related to neuroplasticity, neurogenesis and cell survival.