Modulation of PKA, PKC, CAMKII, ERK 1/2 pathways is involved in the acute antidepressant-like effect of in mice

• Published in: Psychopharmacology 2017-02, Vol.234 (4), p.717
• Main Authors: Pinto Brod, Lucimar M, Fronza, Mariana G, Vargas, Jaqueline Pinto, Lüdtke, Diogo S, Brüning, César Augusto, Savegnago, Lucielli
• Format: Article
• Language: English
• Subjects: Antidepressants; Calmodulin; Extracellular signal-regulated kinases; Health aspects; Organoselenium compounds; Physiological aspects; Protein kinases
• ISSN: 0033-3158
• DOI: 10.1007/s00213-016-4505-5

Rationale (Octylseleno)-xylofuranoside (OSX) is an organoselenium compound from the class of alkylseleno carbohydrates possessing a C8 alkyl chain. Members of this class of organoselenium compounds have promising pharmacological activities, among them are antioxidant and acute antidepressant-like activities with the involvement of monoaminergic system, as previously presented by our research group. Objective The objective of the study was to investigate the possible involvement of cellular signalling pathways in the antidepressant-like effect caused by OSX (0.01 mg/kg, oral route (p.o.) by gavage) in the tail suspension test (TST) in mice. Methods Mice were treated by intracerebroventricular (i.c.v.) injection either with vehicle or with H-89 (1 [mu]g/site i.c.v., an inhibitor of protein kinase A-PKA), KN-62 (1 [mu]g/site i.c.v., an inhibitor of Ca.sup.2+/calmodulin-dependent protein kinase II-CAMKII), chelerythrine (1 [mu]g/site i.c.v., an inhibitor of protein kinase C-PKC) or PD098059 (5 [mu]g/site i.c.v., an inhibitor of extracellular-regulated protein kinase 1/2-ERK.sub.1/2). Fifteen minutes after, vehicle or OSX was injected, and 30 min later, the TST and open field tests (OFT) were carried out. Results The antidepressant-like effect of orally administered OSX was blocked by treatment of the mice with H-89, KN-62, chelerythrine and PD098059; all inhibitors of signalling proteins involved with neurotrophic signalling pathways. The number of crossings in the OFT was not altered by treatment with OSX and/or signalling antagonists. Conclusions The results demonstrated that OSX showed an antidepressant-like effect in the TST in mice through the activation of protein kinases PKA, PKC, CAMKII and ERK1/2 that are involved in intracellular signalling pathways.