Ursolic acid affords antidepressant-like effects in mice through the activation of PKA,PKC,CAMK-II and MEK1/2

Background ursolic acid has been shown to display antidepressant-like effects in mice through the modulation of monoaminergic systems. in this study,we sought to investigate the involvement of signaling pathways on the antidepressant-like effects of ursolic acid. methods mice were treated orally with ursolic acid (0.1 mg/kg) and,45 min later they received the followings inhibitors by intracerebroventricular route: h-89 (pka inhibitor,1 μg/mouse),kn-62 (camk-ii inhibitor,1 μg/mouse),chelerythrine (pkc inhibitor,1 μg/mouse),u0126 (mek1/2 inhibitor,5 μg/mouse),pd98059 (mek1/2 inhibitor,5 μg/mouse),wortmannin (pi3k irreversible inhibitor,0.1 μg/mouse) or ly294002 (pi3k inhibitor,10 nmol/mouse). immobility time of mice was registered in the tail suspension test (tst). results the anti-immobility effect of ursolic acid in the tst was abolished by the treatment of mice with h-89,kn-62,chelerythrine,u0126 or pd98059,but not with wortmannin or ly294002. conclusions these results suggest that activation of pka,pkc,camk-ii,mek1/2 may underlie the antidepressant-like effects of ursolic acid. © 2017 institute of pharmacology,polish academy of sciences