Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test

Eur J Pharmacol. 2013 Jan 5;698(1-3):286-91. doi: 10.1016/j.ejphar.2012.11.003. Epub 2012 Nov 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Hesperidin / pharmacology*
  • Male
  • Mice
  • Naloxone / pharmacology
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism*
  • Receptors, Purinergic P1 / metabolism
  • Swimming*

Substances

  • Antidepressive Agents
  • Receptors, Opioid, kappa
  • Receptors, Purinergic P1
  • Naloxone
  • Naltrexone
  • Hesperidin
  • naltrindole