title: Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice.
abstract: The present study investigated a possible antidepressant-like activity of hesperidin using two predictive tests for antidepressant effect in mice: the forced swimming test (FST) and the tail suspension test (TST). Results demonstrated that hesperidin (0.1, 0.3 and 1 mg/kg, intraperitoneal, i.p.) decreased the immobility time in the FST and TST without affecting the locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) on the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (pCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) and WAY100635 (0.1 mg/kg, subcutaneous, s.c., a selective 5-HT(1A) receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an α(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α(2)-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), AMPT (100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist) or MDL72222 (1 mg/kg, i.p., a 5-HT(3) receptor antagonist) did not block the antidepressant-like effect of hesperidin (0.3 mg/kg, i.p.) in the TST. Administration of hesperidin (0.01 mg/kg, i.p.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. The antidepressant-like effect caused by hesperidin in mice in the TST was dependent on an interaction with the serotonergic 5-HT(1A) receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like property and may be of interest source for therapeutic agent for the treatment of depressive disorders.
authors.affiliation: Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas - LaftamBio Pampa - Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Souza
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: de Gomes
authors.forename: André T R
authors.initials: AT
authors.lastname: Goes
authors.forename: Lucian
authors.initials: L
authors.lastname: Del Fabbro
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Filho
authors.forename: Silvana P
authors.initials: SP
authors.lastname: Boeira
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006569:Hesperidin / Q000494:pharmacology / Q000627:therapeutic use*; D019417:Hindlimb Suspension; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D006569:Hesperidin; D011224:Prazosin