Modulation of PKA, PKC, CAMKII, ERK 1/2 pathways is involved in the acute antidepressant-like effect of (octylseleno)-xylofuranoside (OSX) in mice.

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 µg/site i.c.v., an inhibitor of protein kinase A-PKA), KN-62 (1 µg/site i.c.v., an inhibitor of Ca2+/calmodulin-dependent protein kinase II-CAMKII), chelerythrine (1 µg/site i.c.v., an inhibitor of protein kinase C-PKC) or PD098059 (5 µg/site i.c.v., an inhibitor of extracellular-regulated protein kinase 1/2-ERK1/2). 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.

Involvement of monoaminergic system in the antidepressant-like effect of (octylseleno)-xylofuranoside in the mouse tail suspension test.

Depression is one of the most commonly diagnosed neuropsychiatric disorders and several studies have demonstrated a role for selenium in mood disorders. For this reason, the present study investigated the role of the monoaminergic system in the antidepressant-like action of (octylseleno)-xylofuranoside (OSX), an organoselenium compound, in the tail suspension test (TST) in mice. For this purpose, OSX (0.001­10 mg/kg) was administered orally (p.o.) 30 min prior to testing, and all of the tested doses reduced the immobility time in the TST without changing the locomotor activity measured in the open field test (OFT). Furthermore, the antidepressant-like effect of OSX (0.01 mg/kg, p.o.) in the TSTwas prevented by pre-treatment in mice with ketanserin (1 mg/kg, intraperitoneal route (i.p.); a 5-HT2A/2C receptor antagonist),WAY100635 (0.1mg/kg, subcutaneous (s.c.); a selective 5-HT1A receptor antagonist), p-chlorophenylalaninemethyl ester-PCPA (100mg/kg, i.p.; a selective inhibitor of tryptophan hydroxylase), prazosin (1 mg/kg, i.p.; an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p.; an α2-adrenoceptor antagonist), SCH233390 (0.05 mg/kg, s.c., a dopaminergic D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopaminergic D2 receptor antagonist), but not with ondansetron (1 mg/kg, i.p.; a selective 5-HT3 receptor antagonist). Taken together, these data demonstrate that OSX has a potent antidepressant like effect in TST at lower doses (0.001­10 mg/kg), which is dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems.