{"title":"Interaction effect of lithium and crocin on memory performance and behavioral functions in rats exposed to chronic unpredictable mild stress.","authors":"Delaram Khastoo, Fatemeh Jafari, Batool Ghorbani Yekta, Mahsa Ale-Ebrahim, Soheila Fazli-Tabaei, Salar Vaseghi","doi":"10.1097/FBP.0000000000000848","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"36 7","pages":"484-499"},"PeriodicalIF":1.6000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Pharmacology","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1097/FBP.0000000000000848","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/3 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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