Khastoo Delaram, Jafari Fatemeh, Ghorbani Yekta Batool, Ale-Ebrahim Mahsa, Fazli-Tabaei Soheila, Vaseghi Salar
Department of Physiology, Faculty of Medicine.
Cognitive and Neuroscience Research Center (CNRC).
Behav Pharmacol. 2025 Oct 1;36(7):484-499. doi: 10.1097/FBP.0000000000000848. Epub 2025 Sep 3.
Chronic unpredictable mild stress (CUMS) is an approved method for the induction of depression in rodents. Lithium, as one of the oldest psychiatric drugs, can induce beneficial effects on mood state under stressful conditions. On the other hand, crocin (active component of Saffron) has antioxidant, procognitive, and mood-enhancer effects. In this study, we aimed to investigate the interaction effect of lithium and crocin on mood disturbances and cognitive impairments induced by CUMS. CUMS was performed for 3 weeks. Lithium (100 mg/kg, i.p.), or crocin (30 mg/kg, i.p.), or combination of both was injected during CUMS period (21 injections). Open field test, hot plate, forced swimming test, shuttle box, and Morris water maze were used to evaluate locomotor activity, pain perception, depressive-like behavior, passive avoidance memory, and spatial memory, respectively. The results showed that lithium decreased locomotion and climbing, increased pain threshold and immobility, and impaired passive avoidance and spatial memory in control rats. CUMS also showed all these effects, with more intensity. However, lithium partly reversed the effect of CUMS on locomotion and spatial memory, and completely restored the effect of CUMS on immobility and passive avoidance memory. Also, lithium did not change the effect of CUMS on pain threshold and climbing. Crocin alone, and in combination with lithium significantly reversed all the effects of CUMS. In conclusion, for the first time, the results of the present research showed that the combination of lithium and crocin leads to stronger therapeutic effects on mood disturbances and cognitive impairments induced by chronic stress.
慢性不可预测轻度应激（CUMS）是一种经认可的诱导啮齿动物抑郁的方法。锂作为最古老的精神科药物之一，在应激条件下可对情绪状态产生有益影响。另一方面，藏红花素（藏红花的活性成分）具有抗氧化、促认知和改善情绪的作用。在本研究中，我们旨在探讨锂和藏红花素对CUMS诱导的情绪障碍和认知损伤的相互作用。进行了3周的CUMS。在CUMS期间（21次注射）注射锂（100mg/kg，腹腔注射）、藏红花素（30mg/kg，腹腔注射）或两者的组合。分别使用旷场试验、热板试验、强迫游泳试验、穿梭箱试验和莫里斯水迷宫来评估运动活性、疼痛感知、抑郁样行为、被动回避记忆和空间记忆。结果显示，锂降低了对照大鼠的运动和攀爬能力，提高了疼痛阈值和不动时间，并损害了被动回避和空间记忆。CUMS也显示出所有这些效应，且程度更强。然而，锂部分逆转了CUMS对运动和空间记忆的影响，并完全恢复了CUMS对不动和被动回避记忆的影响。此外，锂没有改变CUMS对疼痛阈值和攀爬的影响。单独使用藏红花素以及与锂联合使用均显著逆转了CUMS的所有效应。总之，本研究结果首次表明，锂和藏红花素的组合对慢性应激诱导的情绪障碍和认知损伤具有更强的治疗效果。
