Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is a highly prescribed antidepressant and is detected at µg/L concentrations in waterways receiving municipal wastewater effluents. We previously showed that early-life venlafaxine exposure disrupted the normal development of the nervous system and reduces larval activity in zebrafish (Danio rerio). However, it is unclear whether the reduced swimming activity may be associated with impaired cardiac function. Here we tested the hypothesis that zygotic exposure to venlafaxine impacts the development and function of the larval zebrafish heart. Venlafaxine (0, 1 or 10 ng) was administered by microinjection into freshly fertilized zebrafish embryos (1-4 cell stage) to assess heart development and function during early-life stages. Venlafaxine deposition in the zygote led to precocious development of the embryo heart, including the timing of the first heartbeat, increased heart size, and a higher heart rate at 24- and 48-hours post-fertilization (hpf). Also, waterborne exposure to environmental levels of this antidepressant during early development increased the heart rate at 48 hpf of zebrafish larvae mimicking the zygotic deposition. The venlafaxine-induced higher heart rate in the embryos was abolished in the presence of NAN-190, an antagonist of the 5HT_1A receptor. Also, heart rate dropped below control levels in the 10 ng, but not 1 ng venlafaxine group at 72 and 96 hpf. An acute stressor reduced the venlafaxine-induced heart rate at 48 hpf but did not affect the already reduced heart rate at 72 and 96 hpf in the 10 ng venlafaxine group. Our results suggest that the higher heart rate in the venlafaxine group may be due to an enhanced serotonin stimulation of the 5HT_1A receptor. Taken together, early-life venlafaxine exposure disrupts cardiac development and has the potential to compromise the cardiovascular performance of larval zebrafish.

文拉法辛是一种选择性 5-羟色胺和去甲肾上腺素再摄取抑制剂，是一种处方量很大的抗抑郁药，在接收市政废水的水道中检测到的浓度为 µg/L。我们之前的研究表明，早期接触文拉法辛会扰乱神经系统的正常发育并降低斑马鱼的幼虫活动（Danio rerio）。然而，尚不清楚游泳活动减少是否与心脏功能受损有关。在这里，我们测试了合子暴露于文拉法辛会影响斑马鱼幼虫心脏发育和功能的假设。文拉法辛（0、1 或 10 ng）通过显微注射注射到新鲜受精的斑马鱼胚胎（1-4 个细胞阶段）中，以评估早期生命阶段的心脏发育和功能。受精卵中的文拉法辛沉积导致胚胎心脏的早熟发育，包括第一次心跳的时间、心脏大小的增加以及受精后 24 和 48 小时 (hpf) 的更高心率。此外，在早期发育过程中水源性暴露于这种抗抑郁药的环境水平会增加斑马鱼幼虫在 48 hpf 时的心率，模仿合子沉积。_1A受体。此外，在 72 和 96 hpf 时，10 纳克文拉法辛组的心率低于对照水平，而 1 纳克文拉法辛组则不然。急性压力源在 48 hpf 时降低了文拉法辛诱导的心率，但不影响 10 ng 文拉法辛组在 72 和 96 hpf 时已经降低的心率。我们的结果表明，文拉法辛组较高的心率可能是由于 5HT _1A受体的血清素刺激增强。总之，生命早期接触文拉法辛会破坏心脏发育，并有可能损害斑马鱼幼虫的心血管功能。