Laboratory of Physiology Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, 89815-899, Brazil.
Laboratory of Translational Psychiatry, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciuma, SC, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Jul;396(7):1423-1433. doi: 10.1007/s00210-023-02406-8. Epub 2023 Feb 3.
Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were as follows: to evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant, and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine (20 mg/kg), imipramine (30 mg/kg), and escitalopram (10 mg/kg). At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 (IL-6) levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.
重度抑郁症（MDD）的病因仍不完全清楚，许多患者对传统治疗方法有抵触情绪。慢性暴露于应激事件可导致疾病的发展和恶化，并与 MDD 的生物学变化有关。在涉及的生物学机制中，炎症变化和氧化平衡与 MDD 的病理生理学有关。喹硫平是一种第二代抗精神病药，可诱导对传统治疗方法无反应的患者产生更好的治疗反应。本研究的主要目的如下：评估慢性轻度应激（CMS）对成年大鼠抑郁样行为、氧化应激和炎症的影响；评估喹硫平的可能的抗抑郁、抗氧化和抗炎作用。动物接受 CMS 方案处理。在 CMS 结束时，动物接受为期 14 天的慢性治疗，药物如下：喹硫平（20mg/kg）、丙咪嗪（30mg/kg）和依地普仑（10mg/kg）。治疗结束后，动物在旷场试验、快感缺失（溅水试验）和强迫游泳中进行评估。行为测试结束后，对动物进行安乐死，并采集血清样本。分析髓过氧化物酶（MPO）活性和白细胞介素 6（IL-6）水平。CMS 诱导大鼠出现抑郁样行为，喹硫平可显著减少这些行为。CMS 动物的血清 MPO 活性和 IL-6 水平升高。喹硫平可显著降低 MPO 活性和 IL-6 水平。这些结果与其他证据一致，表明慢性应激是抑郁症病因学中的一个重要现象，并表明喹硫平通过降低氧化和炎症机制产生抗抑郁作用。
