Insufficient zinc and folic acid levels are associated with depression and poor response to antidepressants. This study aimed to investigate the influences of combined zinc and folic acid replenishment on the anti-depressive effect of paroxetine. Male rats were randomly divided into five groups: control (C), model (M), paroxetine (MP), zinc + folic acid (MZnF), and zinc + folic acid + paroxetine (MZnFP) groups. Rats were exposed to mild unpredictable stress for 3 weeks as a depression model. The combinations of drug and supplements were applied via daily gavage for 4 weeks. The open field test was conducted to observe behavioral changes. A chemiluminescence method was used to detect folacin, and inductively coupled plasma mass spectrometry was used to detect serum elements. Supplementation of zinc and folic acid significantly improved behavior responses to paroxetine, including movement speed, total distance, and central zone frequency. In addition, higher calcium and copper levels and a lower arsenic level were found in the serum of the MZnFP group. Thus, supplementation of zinc and folacin can enhance the anti-depressive effect of paroxetine, and the mechanism is potentially related to the improved levels of calcium and copper and a reduced level of arsenic.

锌和叶酸水平不足与抑郁症和对抗抑郁药的不良反应有关。这项研究旨在探讨锌和叶酸联合补充对帕罗西汀抗抑郁作用的影响。将雄性大鼠随机分为五组：对照组（C），模型（M），帕罗西汀（MP），锌+叶酸（MZnF）和锌+叶酸+帕罗西汀（MZnFP）组。将大鼠作为抑郁模型暴露于轻度不可预测的压力下3周。通过每日管饲法将药物和补品的组合应用4周。进行野外试验以观察行为变化。化学发光法用于检测叶黄素，电感耦合等离子体质谱法用于检测血清元素。补充锌和叶酸可显着改善对帕罗西汀的行为反应，包括运动速度，总距离和中心区频率。另外，在MZnFP组的血清中发现较高的钙和铜水平和较低的砷水平。因此，锌和叶酸的补充可以增强帕罗西汀的抗抑郁作用，其机理可能与钙和铜水平的提高以及砷水平的降低有关。