title: Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test.
abstract: The opioid system has been implicated as a contributing factor for major depression and is thought to play a role in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of hesperidin in the mouse forced swimming test. Our results demonstrate that hesperidin (0.1, 0.3 and 1 mg/kg; intraperitoneal) decreased the immobility time in the forced swimming test without affecting locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) in the forced swimming test was prevented by pretreating mice with naloxone (1 mg/kg, a nonselective opioid receptor antagonist) and 2-(3,4-dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl] acetamide (DIPPA (1 mg/kg), a selective κ-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, a peripherally acting opioid receptor antagonist), naltrindole (3 mg/kg, a selective δ-opioid receptor antagonist), clocinnamox (1 mg/kg, a selective μ-opioid receptor antagonist) or caffeine (3 mg/kg, a nonselective adenosine receptor antagonist). In addition, a sub-effective dose of hesperidin (0.01 mg/kg) produced a synergistic antidepressant-like effect in the forced swimming test when combined with a sub-effective dose of morphine (1 mg/kg). The antidepressant-like effect of hesperidin in the forced swimming test on mice was dependent on its interaction with the κ-opioid receptor, but not with the δ-opioid, μ-opioid or adenosinergic receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like properties and may be of interest as a 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: Carlos B
authors.initials: CB
authors.lastname: Filho
authors.forename: Lucian
authors.initials: L
authors.lastname: Del Fabbro
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: de Gomes
authors.forename: André T R
authors.initials: AT
authors.lastname: Goes
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Souza
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*; D001522:Behavior, Animal / Q000187:drug effects; D006569:Hesperidin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D017473:Receptors, Opioid, kappa; D018047:Receptors, Purinergic P1; D009270:Naloxone; D009271:Naltrexone; D006569:Hesperidin; C055382:naltrindole