title: Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice.
abstract: 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.
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Franciele
authors: F
authors: Donato
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Carlos
authors: C
authors: Borges Filho
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Renata
authors: R
authors: Giacomeli
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Elza Eliza Tenório
authors: EE
authors: Alvater
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Lucian
authors: L
authors: Del Fabbro
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Michele da Silva
authors: Mda S
authors: Antunes
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Marcelo Gomes
authors: MG
authors: de Gomes
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: André Tiago Rossito
authors: AT
authors: Goes
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Leandro Cattelan
authors: LC
authors: Souza
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Silvana Peterini
authors: SP
authors: Boeira
authors: Laboratory of Pharmacological and Toxicological Assessments Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa , Itaqui, Rio Grande do Sul, Brazil .
authors: Cristiano Ricardo
authors: CR
authors: Jesse
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001030:Apamin / Q000008:administration & dosage; D001120:Arginine / Q000494:pharmacology; D018999:Charybdotoxin / Q000008:administration & dosage; D004357:Drug Synergism; D005905:Glyburide / Q000008:administration & dosage; D006569:Hesperidin / Q000008:administration & dosage / Q000494:pharmacology*; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000008:administration & dosage
chemical_list: D000928:Antidepressive Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D001120:Arginine; D006569:Hesperidin; D005905:Glyburide
keywords: depression; flavonoid; mechanisms of action; nitric oxide; serotonin
references: Psychopharmacology (Berl). 1985;85(3):367-70
references: 3923523
references: Proc Natl Acad Sci U S A. 1982 Feb;79(4):1308-12
references: 6122211
references: Neuroscience. 1993 Jan;52(1):191-205
references: 7679479
references: J Pharmacol Exp Ther. 1997 Jul;282(1):262-70
references: 9223563
references: Br J Pharmacol. 1999 Apr;126(7):1653-9
references: 10323599
references: J Physiol. 1999 Jun 1;517 ( Pt 2):385-90
references: 10332089
references: Eur J Pharmacol. 2005 Apr 11;512(2-3):189-98
references: 15840404
references: Pharmacol Biochem Behav. 2005 Sep;82(1):156-62
references: 16153700
references: Psychopharmacology (Berl). 2006 Apr;185(3):298-305
references: 16518647
references: Eur J Pharmacol. 2008 May 31;586(1-3):114-22
references: 18367171
references: J Agric Food Chem. 2008 Feb 13;56(3):859-64
references: 18189359
references: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):690-6
references: 17296254
references: Eur J Neurosci. 2008 Jun;27(11):2783-802
references: 18588525
references: Neuron. 2008 Nov 26;60(4):642-56
references: 19038221
references: Eur J Pharmacol. 2009 Jun 24;613(1-3):74-8
references: 19406118
references: Life Sci. 2010 Feb 27;86(9-10):372-6
references: 20102723
references: J Agric Food Chem. 2012 Jan 11;60(1):522-32
references: 22098419
references: Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10;40:103-9
references: 22996046
references: Eur J Pharmacol. 2013 Jan 5;698(1-3):286-91
references: 23178563
references: J Med Food. 2013 Nov;16(11):1030-8
references: 24236576
references: Nat Commun. 2014;5:3106
references: 24469021
references: Brain Res Bull. 2014 May;104:19-26
references: 24709058
references: Neuropharmacology. 2001 Aug;41(2):175-85
references: 11489454
references: Trends Pharmacol Sci. 2002 May;23(5):238-45
references: 12008002
references: Neurosci Lett. 2003 May 29;343(1):1-4
references: 12749983
references: Brain Res. 2004 Aug 27;1018(2):201-7
references: 15276879
references: J Pharmacol Exp Ther. 1991 Jan;256(1):371-7
references: 1846422