Rahman Havizur, Anggadiredja Kusnandar, Sasongko Lucy
Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Bandung 41116, Indonesia.
Department of Pharmacy, Faculty of Medicine and Health Sciences, University of Jambi, Jambi 36361, Indonesia.
Toxicol Rep. 2025 Jan 20;14:101920. doi: 10.1016/j.toxrep.2025.101920. eCollection 2025 Jun.
Prolonged administration of antibiotics may be associated with depression due to the potential risk of dysbiosis. Thus, the restoration of microbial balance, through administration of prebiotics, might overcome the problem. This study investigated the mechanisms of antibiotic-induced depression, which were explored through statistical correlation analysis. The potential benefit of lactulose, a prebiotic, on this behavioral disorder was further assessed. The rats were assigned to groups receiving 102.8 mg/kg ciprofloxacin daily for 1, 8, 15, or 22 days. A different group of rat was given the same regimen for 8 days accompanied with lactulose at 2056 mg/kg. Upon completion of ciprofloxacin administration, the rats were tested for depression-like behavior (forced swimming test, FST; and sucrose preference test, SPT). They were then sacrificed for biochemical assessment in the hippocampus and prefrontal cortex. The mechanism studies revealed significant correlation between SPT vs. serotonin in the hippocampus, and SPT vs. serotonin, cortisol, NF-κB in the prefrontal cortex. Meanwhile, FST was significantly correlated with serotonin in the hippocampus and the prefrontal cortex, while in the prefrontal cortex it was significantly correlated with cortisol, NF-κB, and IL-6. Based on the afore-mentioned results, it was found that lactulose improved FST by targeting serotonin in the hippocampus. This study indicate that ciprofloxacin induce depression-like behavior via modulation of several neurotransmitter system as well as proinflammatory cytokines in the hippocampus and prefrontal cortex. The results further suggest the potential of lactulose to improve this behavior.
由于存在微生物群失调的潜在风险，长期使用抗生素可能与抑郁症有关。因此，通过服用益生元来恢复微生物平衡，可能会解决这个问题。本研究通过统计相关性分析，探究了抗生素诱发抑郁症的机制。进一步评估了益生元乳果糖对这种行为障碍的潜在益处。将大鼠分为四组，分别每日接受102.8mg/kg环丙沙星，持续1、8、15或22天。另一组大鼠接受相同方案8天，并同时服用2056mg/kg乳果糖。环丙沙星给药结束后，对大鼠进行抑郁样行为测试（强迫游泳试验，FST；和蔗糖偏好试验，SPT）。然后将它们处死，对海马体和前额叶皮质进行生化评估。机制研究表明，SPT与海马体中的血清素、前额叶皮质中的血清素、皮质醇、NF-κB之间存在显著相关性。同时，FST与海马体和前额叶皮质中的血清素显著相关，而在前额叶皮质中，它与皮质醇、NF-κB和IL-6显著相关。基于上述结果，发现乳果糖通过作用于海马体中的血清素改善了FST。本研究表明，环丙沙星通过调节海马体和前额叶皮质中的几种神经递质系统以及促炎细胞因子，诱发抑郁样行为。结果进一步表明了乳果糖改善这种行为的潜力。
