Venlafaxine plus melatonin ameliorate reserpine-induced depression-like behavior in zebrafish

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.