Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas - LaftamBio Pampa - Universidade Federal do Pampa, CEP 97650-000, Itaqui, RS, Brazil.
Eur J Pharmacol. 2013 Jan 5;698(1-3):286-91. doi: 10.1016/j.ejphar.2012.11.003. Epub 2012 Nov 20.
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.
阿片系统被认为是导致重度抑郁症的一个因素，并且被认为在抗抑郁药的作用机制中发挥作用。本研究探讨了橙皮苷在小鼠强迫游泳试验中抗抑郁样作用与阿片系统的关系。我们的结果表明，橙皮苷（0.1、0.3 和 1mg/kg；腹腔内给药）可减少强迫游泳试验中的不动时间，而不影响旷场试验中的运动活性。橙皮苷（0.3mg/kg）在强迫游泳试验中的抗抑郁样作用可被纳洛酮（1mg/kg，一种非选择性阿片受体拮抗剂）和 2-（3,4-二氯苯基）-Nmethyl-N-[(1S)-1-（3-异硫氰酸根合苯基）-2-（1-吡咯烷基）乙基]乙酰胺（DIPPA（1mg/kg），一种选择性 κ-阿片受体拮抗剂）预处理而阻断，但不能被纳洛酮甲碘化物（1mg/kg，一种外周阿片受体拮抗剂）、naltrindole（3mg/kg，一种选择性 δ-阿片受体拮抗剂）、clocinnamox（1mg/kg，一种选择性 μ-阿片受体拮抗剂）或咖啡因（3mg/kg，一种非选择性腺苷受体拮抗剂）阻断。此外，橙皮苷的亚有效剂量（0.01mg/kg）与亚有效剂量的吗啡（1mg/kg）联合使用时，在强迫游泳试验中产生协同抗抑郁样作用。橙皮苷在强迫游泳试验中对小鼠的抗抑郁样作用依赖于其与 κ-阿片受体的相互作用，而不依赖于 δ-、μ-或腺苷能受体。综上所述，这些结果表明橙皮苷具有抗抑郁样特性，可能作为治疗抑郁障碍的治疗剂具有一定的研究价值。
