The present study was designed to investigate the putative effect of vitexin, a flavone C-glucoside present in some drugs, medicinal plants and nutraceuticals, on the central nervous system. Vitexin (10-30 mg/kg) did not show significant alterations in the behaviour of mice tested in hole-board, plus-maze or activity cage tests. However, immobility time of the mice significantly reduced by vitexin administrations in both the tail-suspension and modified forced swimming tests. The anti-immobility effect of vitexin in the tail-suspension test was reversed with alpha-methyl-para-tyrosine methyl ester (AMPT, an inhibitor of catecholamine synthesis, 100 mg/kg, i.p.), yohimbine (an alpha(2)-adrenoceptor antagonist, 1 mg/kg, i.p.), NAN 190 (a 5-HT1A antagonist, 0.5 mg/kg, i.p.), SCH 23390 (a dopamine D-1 antagonist, 0.05 mg/kg, s.c.) and sulpiride (a dopamine D-2/D-3 antagonist, 50 mg/kg, i.p.). The same effect was not reversed, however, by p-chlorophenylalanine methyl ester (PCPA; an inhibitor of serotonin synthesis 100 mg/kg, i.p., administered for 4 consecutive days), ketanserin (a 5-HT2A/2C antagonist, 1-4 mg/kg, i.p.), ondansetron (a 5-HT3 antagonist, 0.1-0.4 mg/kg, i.p.), prazosin (an alpha(1)-adrenoceptor antagonist, 1-4 mg/kg, i.p.), or propranolol (a non-selective beta-adrenoceptor antagonist, 5-20 mg/kg, i.p.). These results suggest that the anti-depressant-like effect of vitexin is mediated through an increase in catecholamine levels in the synaptic cleft as well as through interactions with the serotonergic 5-HT1A, noradrenergic alpha(2), and dopaminergic D-1, D-2, and D-3 receptors. To our knowledge, this is the first study to show findings that indicate an anti-depressant-like effect of vitexin and its underlying mechanisms. (C) 2012 Elsevier B.V. All rights reserved.