Involvement of PKA, PKC, CAMK-II and MEK1/2 in the acute antidepressant-like effect of creatine in mice

Background: The aim of this study was to investigate the involvement of signaling pathways on the creatine antidepressant-like effect in the tail suspension test (TST) in mice. Methods: The TST was used to assess the antidepressant-like properties of creatine. Results: The anti-immobility effect of creatine (1 mg/kg, p.o.) in the TST was blocked by i.c.v. pretreatment with H-89 (1 mu g/site, PKA inhibitor), KN-62 (1 mu g/site, CAMK-II inhibitor), chelerythrine (1 mu g/site, PKC inhibitor), U0126 (5 mu g/site, MEK1/2 inhibitor) or P009058 (5 mu g/site, MEK1/2 inhibitor). Conclusion: These results suggest that the antidepressant-like effect of creatine is dependent on PKA, CaMK-II, PKC and MEK 1/2 activation. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. Z o.o. All rights reserved.