Major depression disorder is a debilitating psychiatric disease affecting millions of people worldwide. This disorder is the leading cause of morbidity and mortality in high-income countries. Selective serotonin reuptake inhibitors such as fluoxetine are first-line drugs for treating depression-related disorders, but not all patients respond well to these antidepressants. This study aimed to evaluate whether fluoxetine combined with aerobic exercise can affect lipopolysaccharide (LPS)-induced depressive-like behavior, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and brain inflammation in mice. Male mice were exposed to fluoxetine, swimming exercise, or a combination of both and finally treated with LPS. We measured depression-related symptoms such as anhedonia, behavioral despair, weight gain, and food intake. Hormones (corticosterone and testosterone) and cytokines (IL-1β, IL-6, TNF-α, IL-10) were also measured in serum and brain (hippocampus and prefrontal cortex), respectively. The findings indicated that LPS induced anhedonia and behavioral despair and increased corticosterone, hippocampal IL-1β, TNF-α, and decreased testosterone and hippocampal IL-10 in mice. Fluoxetine and exercise separately reduced LPS-induced depressive-like behavior, while their combination synergistically reduced these symptoms in LPS-treated mice. We found fluoxetine alone increased food intake and body weight in LPS-treated mice. Fluoxetine and exercise combination reduced corticosterone, hippocampal TNF-α, and prefrontal IL-6 and TNF-α levels and increased testosterone and hippocampal and prefrontal IL-10 levels more effectively than fluoxetine alone in LPS-treated mice. This study suggests that swimming exercise combined with fluoxetine can affect depression-related behavior, HPA axis, and brain inflammation more effectively than when they are used separately.

重度抑郁症是一种使人衰弱的精神疾病，影响着全世界数百万人。这种疾病是高收入国家发病和死亡的主要原因。选择性血清素再摄取抑制剂（例如氟西汀）是治疗抑郁症相关疾病的一线药物，但并非所有患者都对这些抗抑郁药反应良好。本研究旨在评估氟西汀联合有氧运动是否可以影响脂多糖（LPS）诱导的抑郁样行为、下丘脑-垂体-肾上腺（HPA）轴失调和小鼠脑炎症。雄性小鼠接受氟西汀、游泳运动或两者的结合，最后接受脂多糖治疗。我们测量了与抑郁症相关的症状，如快感缺乏、行为绝望、体重增加和食物摄入量。还分别测量了血清和大脑（海马和前额皮质）中的激素（皮质酮和睾酮）和细胞因子（IL-1β、IL-6、TNF-α、IL-10）。研究结果表明，LPS 会导致小鼠快感缺乏和行为绝望，并增加皮质酮、海马 IL-1β、TNF-α，并降低睾酮和海马 IL-10。氟西汀和运动分别减少 LPS 诱导的抑郁样行为，而它们的组合可协同减少 LPS 治疗小鼠的这些症状。我们发现单独使用氟西汀可以增加 LPS 治疗小鼠的食物摄入量和体重。在 LPS 处理的小鼠中，氟西汀和运动组合比单独使用氟西汀更有效地降低皮质酮、海马 TNF-α 以及前额叶 IL-6 和 TNF-α 水平，并增加睾酮、海马和前额叶 IL-10 水平。这项研究表明，游泳运动与氟西汀相结合，比单独使用时更能有效地影响抑郁相关行为、HPA 轴和脑部炎症。