Hajmirzaeyian Arwin, Chamanara Mohsen, Rashidian Amir, Shakyba Saied, Nassireslami Ehsan, Akhavan-Sigari Reza
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
Heliyon. 2021 Jan 11;7(1):e05900. doi: 10.1016/j.heliyon.2021.e05900. eCollection 2021 Jan.
It has been well documented that administration of melatonin could reveal antidepressant-like effect in rodents. However, the protective effect of melatonin on stress-induced depression/anxiety and its underlying mechanism is yet to be understood. In this regard, in the current study, acute foot-shock stress (FSS) was used to evaluate the antidepressant-like effect of melatonin on neurogenic stress-induced depression in mice. Behavioral evaluation was done by using the forced swimming test (FST) and Open-field test (OFT). Melatonin, MK-801, and ketamine (NMDA receptor antagonists), and NMDA (NMDA receptor agonist) were used to elucidate any association between melatonin and NMDA pathway in behavioral despair induced by acute-FSS. Applying acute-FSS to mice significantly induced depressant-like behavior in FST without any significant impact on locomotor activity in the OFT. We observed that melatonin (dose-dependently) significantly improved the depressant-like effect of FSS, but it did not impact the locomotion in animals. Acute injection of MK-801 at sub-effective doses (0.01 mg/kg) or ketamine (0.1 mg/kg) potentiated the antidepressant-like effect of a sub-effective dose of melatonin. However, the sub-effective dose of NMDA (30 mg/kg) abolished the protective effect of melatonin on the behavioral profile of stressed animals. Our results could reflect the antidepressant-like effect of melatonin on neurogenic stress-induced depressive behaviors in mice. Also, our results showed that NMDA receptors could be involved in the antidepressant-like effect of melatonin.
已有充分文献证明，褪黑素给药可在啮齿动物中显示出抗抑郁样作用。然而，褪黑素对应激诱导的抑郁/焦虑的保护作用及其潜在机制尚待了解。在这方面，在本研究中，急性足部电击应激（FSS）被用于评估褪黑素对小鼠神经源性应激诱导抑郁的抗抑郁样作用。行为评估通过强迫游泳试验（FST）和旷场试验（OFT）进行。褪黑素、MK-801和氯胺酮（NMDA受体拮抗剂）以及NMDA（NMDA受体激动剂）被用于阐明褪黑素与急性FSS诱导的行为绝望中NMDA途径之间的任何关联。对小鼠施加急性FSS可显著诱导FST中的抑郁样行为，而对OFT中的运动活动没有任何显著影响。我们观察到，褪黑素（剂量依赖性地）显著改善了FSS的抑郁样作用，但对动物的运动没有影响。以亚有效剂量（0.01mg/kg）急性注射MK-801或氯胺酮（0.1mg/kg）可增强亚有效剂量褪黑素的抗抑郁样作用。然而，亚有效剂量的NMDA（30mg/kg）消除了褪黑素对应激动物行为特征的保护作用。我们的结果可以反映褪黑素对小鼠神经源性应激诱导的抑郁行为的抗抑郁样作用。此外，我们的结果表明，NMDA受体可能参与了褪黑素的抗抑郁样作用。
