KMID : 1161420150180070818
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Journal of Medicinal Food 2015 Volume.18 No. 7 p.818 ~ p.823
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Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice
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Donato Franciele
Filho Carlos Borges Giacomeli Renata Alvater Elza Eliza Tenorio Del Fabbro Lucian da Silva Antunes Michele de Gomes Marcelo Gomes Goes Andre Tiago Rossito Souza Leandro Cattelan Boeira Silvana Peterini Jesse Cristiano Ricardo
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Abstract
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The administration of hesperidin elicits an antidepressant-like effect in mice by a mechanism dependent on an interaction with the l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, whose stimulation is associated with the activation of potassium (K+) channels. Thus, this study investigated the involvement of different types of K+ channels in the antidepressant-like effect of hesperidin in the mice tail suspension test (TST). The intracerebroventricular administration of tetraethylammonium (TEA, a nonspecific blocker of K+ channels), glibenclamide (an ATP-sensitive K+ channel blocker), charybdotoxin (a large- and intermediate-conductance calcium-activated K+ channel blocker) or apamin (a small-conductance calcium-activated K+ channel blocker) combined with a subeffective dose of hesperidin (0.01?mg/kg, intraperitoneally [i.p.]) was able to produce a synergistic antidepressant-like effect in the mice TST. Moreover, the antidepressant-like effect elicited by an effective dose of hesperidin (0.3?mg/kg, i.p.) in TST was abolished by the treatment of mice with pharmacological compounds K+ channel openers (cromakalim and minoxidil). Results showed that the antidepressant-like effect of hesperidin in TST may involve, at least in part, the modulation of neuronal excitability through inhibition of K+ channels and may act through a mechanism dependent on the inhibition of l-arginine-NO pathway.
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KEYWORD
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depression, flavonoid, mechanisms of action, nitric oxide, serotonin
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