Laaziz Abderrahim, El Mostafi Hicham, Elhessni Aboubaker, Touil Tarik, Doumar Hanane, Mesfioui Abdelhalem
Biology and Health Laboratory, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco.
Higher Institute of Nursing and Health Professions of Rabat, Morocco.
IBRO Neurosci Rep. 2022 Aug 1;13:147-155. doi: 10.1016/j.ibneur.2022.07.007. eCollection 2022 Dec.
Corticosteroids are widely used in medicine, for their anti-inflammatory and immunosuppressive actions, but can lead to troubling psychiatric side-effects. In fact, corticosteroids can induce many symptoms and syndromes, for example, mood disorders, anxiety and panic disorder, suicidal thinking and behavior. Furthermore, chronic stress and the administration of exogenous glucocorticoids are reported to induce affective changes in humans and rodents that relate to depressive state. Animal models are highly useful tools for studying the depression etiology. Face validity, construct validity, and predictive validity are the main criteria to evaluate animal depression models. The present study aimed to investigate the behavioral, cognitive, and biochemical effects of a chronic administration of DEX on Wistar rats. Wistar rats were administered daily with DEX (1.5 mg/kg, i.p., 21 days) or saline, the clomipramine treatment (2 mg/kg, i.p.) was realized just after the DEX injections for 21 days. DEX induced changes were evaluated by: forced swimming, novelty suppressed feeding, saccharin preference, open field, Morris water maze, and oxidative stress state in the brain. Results showed that chronic DEX administration conduct to a range of depression-related behavioral traits, including anhedonia, despair, weight loss, anxiety-like behavior, and cognitive impairments, which fill the face validity criterion. The DEX induced behavioral changes may result from the massive production of oxidative stress agents. This sustains the etiological hypothesis claiming that hyper-circulating glucocorticoid resulting from HPA dysfunction induces damage in certain neural structures related to depressive disorder, essentially the hippocampus. The antidepressant treatment has restored the behavioral state of rats which fills the predictive validity criterion.
皮质类固醇因其抗炎和免疫抑制作用而在医学中广泛应用，但可能导致令人困扰的精神副作用。事实上，皮质类固醇可诱发多种症状和综合征，例如情绪障碍、焦虑和惊恐障碍、自杀性思维和行为。此外，据报道，慢性应激和外源性糖皮质激素的给药会在人类和啮齿动物中诱发与抑郁状态相关的情感变化。动物模型是研究抑郁症病因的非常有用的工具。表面效度、结构效度和预测效度是评估动物抑郁模型的主要标准。本研究旨在调查长期给予地塞米松（DEX）对Wistar大鼠行为、认知和生化方面的影响。Wistar大鼠每天腹腔注射DEX（1.5毫克/千克，共21天）或生理盐水，在注射DEX 21天后立即进行氯米帕明治疗（2毫克/千克，腹腔注射）。通过强迫游泳、新奇抑制摄食、糖精偏好、旷场试验、莫里斯水迷宫试验以及大脑氧化应激状态来评估DEX诱导的变化。结果表明，长期给予DEX会导致一系列与抑郁相关的行为特征，包括快感缺失、绝望、体重减轻、焦虑样行为和认知障碍，这符合表面效度标准。DEX诱导的行为变化可能是由氧化应激因子的大量产生所致。这支持了病因学假说，即声称由下丘脑 - 垂体 - 肾上腺（HPA）功能障碍导致的糖皮质激素循环过多会损害某些与抑郁症相关的神经结构，主要是海马体。抗抑郁治疗恢复了大鼠的行为状态，这符合预测效度标准。
