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咖啡因与睡眠剥夺对小鼠旷场行为、应激反应及抗氧化状态的影响

Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice.

作者信息

Onaolapo J Olakunle, Onaolapo Y Adejoke, Akanmu A Moses, Olayiwola Gbola

机构信息

Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Osogbo, Osun, Nigeria.

Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.

出版信息

Sleep Sci. 2016 Jul-Sep;9(3):236-243. doi: 10.1016/j.slsci.2016.10.008. Epub 2016 Nov 12.

Abstract

OBJECTIVES

Effects of daily caffeine consumption on open-field behaviours, serum corticosterone and brain antioxidant levels were investigated after six hours of total sleep-deprivation in prepubertal mice. We tested the hypothesis that daily caffeine consumption may significantly alter behaviour, stress and antioxidative response of prepubertal mice to an acute episode of total sleep-deprivation.

METHODS

Prepubertal Swiss mice of both sexes were assigned to two main groups of 120 each (subdivided into 6 groups of 10 each, based on sex), and administered vehicle or graded oral doses of caffeine (10, 20, 40, 80 and 120 mg/kg/day) for 14 days. On day 14, a main group was subjected to 6 h of total sleep-deprivation by 'gentle-handling'. Open-field behaviours were then assessed in both groups, after which animals were euthanized, and levels of corticosterone, superoxide dismutase and glutathione peroxidase assayed.

RESULTS

Horizontal locomotion, rearing and grooming increased significantly, compared to control, with sleep-deprived (SD) mice showing stronger caffeine-driven responses at higher doses; and SD female mice showing sustained response to caffeine, compared to respective males. Plasma corticosterone increased with increasing doses of caffeine in both non sleep-deprived (NSD) and SD mice; although SD mice had higher corticosterone levels. Sleep-deprivation and/or higher doses of caffeine were associated with derangements in brain antioxidant levels.

CONCLUSION

Repeated caffeine consumption and/or acute sleep-deprivation led to significant changes in pattern of open-field behaviour and stress/antioxidant response in mice. Responses seen in the study are probably due to modulatory effects of caffeine on the total body response to stressful stimuli.

摘要

目的

研究青春期前小鼠在完全睡眠剥夺6小时后,每日摄入咖啡因对旷场行为、血清皮质酮和脑抗氧化水平的影响。我们检验了这样一个假设,即每日摄入咖啡因可能会显著改变青春期前小鼠对急性完全睡眠剥夺事件的行为、应激和抗氧化反应。

方法

将青春期前的瑞士雌雄小鼠各分为两个主要组,每组120只(根据性别再细分为每组10只的6个小组),并给予溶媒或不同梯度口服剂量的咖啡因(10、20、40、80和120毫克/千克/天),持续14天。在第14天,对一个主要组通过“轻柔处理”进行6小时的完全睡眠剥夺。然后评估两组的旷场行为,之后对动物实施安乐死,并检测皮质酮、超氧化物歧化酶和谷胱甘肽过氧化物酶的水平。

结果

与对照组相比,水平运动、竖毛和理毛显著增加,睡眠剥夺(SD)小鼠在较高剂量时对咖啡因的反应更强;与相应雄性小鼠相比,SD雌性小鼠对咖啡因的反应持续存在。在非睡眠剥夺(NSD)和SD小鼠中,血浆皮质酮均随咖啡因剂量增加而升高;尽管SD小鼠的皮质酮水平更高。睡眠剥夺和/或较高剂量的咖啡因与脑抗氧化水平紊乱有关。

结论

重复摄入咖啡因和/或急性睡眠剥夺导致小鼠旷场行为模式以及应激/抗氧化反应发生显著变化。本研究中观察到的反应可能是由于咖啡因对机体对应激刺激的整体反应具有调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b03/5241623/fbb08a11a452/gr1.jpg

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