Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test
Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test
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DOI：
10.1016/j.ejphar.2012.11.003
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发表时间：
2013-01-05
影响因子：
5
通讯作者：
Jesse, Cristiano R.
中科院分区：
文献类型：
--
作者：
Filho, Carlos B.;Del Fabbro, Lucian;Jesse, Cristiano R.
阿片系统被认为是重度抑郁症的一个促成因素，并被认为在抗抑郁药的作用机制中发挥作用。本研究在小鼠强迫游泳实验中探讨了阿片系统参与橙皮苷抗抑郁样作用的机制。我们的研究结果表明，橙皮苷（0.1，0.3和1毫克/公斤;腹腔注射）减少不动时间在强迫游泳试验中，而不影响运动活动在开放领域的测试。橙皮苷的抗抑郁样作用纳洛酮预处理可阻止小鼠强迫游泳实验中的（1 mg/kg，非选择性阿片受体拮抗剂）和2-（3，4-二氯苯基）-N-甲基-N-[（1 S）-1-（3-异硫氰酸基苯基）-2-（1-吡咯烷基）乙基]乙酰胺（DIPPA（1 mg/kg），一种选择性κ-阿片受体拮抗剂），但不与纳洛酮甲碘化（1 mg/kg，外周作用阿片受体拮抗剂）、纳曲吲哚（3 mg/kg，选择性δ-阿片受体拮抗剂）、clocinnamox（1 mg/kg，选择性μ-阿片受体拮抗剂）或咖啡因（3 mg/kg，非选择性腺苷受体拮抗剂）。此外，当与次有效剂量的吗啡（1 mg/kg）组合时，次有效剂量的橙皮苷（0.01 mg/kg）在强迫游泳试验中产生协同抗抑郁样作用。橙皮苷在小鼠强迫游泳试验中的抗抑郁样作用依赖于其与κ阿片受体的相互作用，而不是与δ阿片受体、μ阿片受体或腺苷能受体的相互作用。综上所述，这些结果表明，橙皮苷具有抗抑郁药样的性质，并可能是一个感兴趣的治疗剂，用于治疗抑郁症。由爱思唯尔公司出版
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 kappa-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, a peripherally acting opioid receptor antagonist), naltrindole (3 mg/kg, a selective delta-opioid receptor antagonist), clocinnamox (1 mg/kg, a selective mu-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 kappa-opioid receptor, but not with the delta-opioid, mu-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. Published by Elsevier B.V.