Venlafaxine (VEN) is one of the first clinical drugs for the treatment of depression. Long-term use may cause a potentially life-threatening serotonin syndrome. Melatonin (MT) could ameliorate depression behavior. Therefore, the aim of this study was to investigate the antidepressant effects of venlafaxine in combination with melatonin on zebrafish. Reserpine was used to induce depression-like behavioral zebrafish. To explore the effects of combined use of venlafaxine and melatonin on depression-like zebrafish induced by reserpine. We tested the depressive behavior of adult zebrafish through a novel tank test, and evaluated the levels of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) in zebrafish brain using enzyme-linked immunosorbent assay (ELISA), besides that the gene expression of serotonin transporters a (serta), dopamine transporters (dat) and norepinephrine transporters (net), vesicular monoamine transporter2 (vmat2) and monoamine oxidase (mao) were evaluated by qRT-PCR. The results showed that, compared with reserpine-only group, venlafaxine (VEN, 0.025 mg/L) and melatonin (MT, 1 μM) increased the parameters of exploration in the top of the tank and decreased freezing behavior significantly. Compared with reserpine-only group, the use of VEN combined with MT increased serotonin and norepinephrine levels significantly, while there was no obvious difference in dopamine content. The results of qRT-PCR showed that the use of VEN combined with MT significantly reduced the expression of serta and promoted the expression of vmat2, but had no significant effect on the expression of net, dat and mao. The results indicated that venlafaxine combined with melatonin showed more effective role to remedy the depressive symptoms in zebrafish, providing a reference for the clinical application of antidepressants.

中文翻译：

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文拉法辛加褪黑素改善了利血平在斑马鱼中引起的抑郁样行为。

Venlafaxine（VEN）是治疗抑郁症的首批临床药物之一。长期使用可能会导致威胁生命的血清素综合症。褪黑激素（MT）可以改善抑郁行为。因此，本研究的目的是研究文拉法辛与褪黑激素联合对斑马鱼的抗抑郁作用。利血平被用于诱导抑郁症样的行为斑马鱼。探讨文拉法辛和褪黑素联合使用对利血平诱导的抑郁样斑马鱼的影响。我们通过新型罐试验测试了成年斑马鱼的抑郁行为，并通过酶联免疫吸附测定（ELISA）评估了斑马鱼大脑中5-羟色胺（5-HT），多巴胺（DA）和去甲肾上腺素（NA）的水平血清素转运蛋白a（serta）的基因表达，通过qRT-PCR评估多巴胺转运蛋白（dat）和去甲肾上腺素转运蛋白（净），水泡单胺转运蛋白2（vmat2）和单胺氧化酶（mao）。结果表明，与仅利血平组相比，文拉法辛（VEN，0.025 mg / L）和褪黑激素（MT，1μM）增加了罐顶部的勘探参数，并显着降低了冷冻行为。与仅利血平组相比，VEN与MT联合使用可显着提高血清素和去甲肾上腺素水平，而多巴胺含量则无明显差异。qRT-PCR结果表明，VEN与MT联合使用可显着降低serta的表达并促进vmat2的表达，但对net，dat和mao的表达无明显影响。