Li Yan, Guo Zhixuan, Cai Chenxi, Liu Danni, Kang Yin, Liu Pengfei
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, 225009, China.
Department of Traditional Chinese Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, 225012, China.
Heliyon. 2023 Feb 28;9(3):e14170. doi: 10.1016/j.heliyon.2023.e14170. eCollection 2023 Mar.
Caffeine is a non-selective adenosine receptor antagonist with pro-arousal and pro-sympathetic nervous system excitatory effects, and these pharmacological effects fit well with the physiological functions of orexin. The purpose of this study was to investigate the role of the orexinergic nervous system in the pharmacological effects of caffeine.
An animal model of sleepiness caused by adenosine accumulation was established by sleep deprivation, and caffeine's effects on the spontaneous activity and sympathetic nervous system of the model animals were evaluated by using the open-field experiment and gastrointestinal peristaltic observation, respectively, and the intervention of orexin receptor antagonists on the pharmacological effects of caffeine was also observed.
Mice with 8 h of sleep deprivation showed a significant decrease in spontaneous activity and a significant increase in gastrointestinal push distance. After caffeine intervention, the spontaneous activities of sleep-deprived mice significantly increased and gastrointestinal peristalsis significantly decreased dose-dependent, while orexin receptors antagonist blocked the pro-arousal and inhibitory gastrointestinal peristalsis effects of caffeine on sleep-deprived mice.
Orexinergic nervous system mediated caffeine's excitatory effects on the pro-arousal and pro-sympathetic nervous systems. Orexin is likely to be an important performer in the pharmacological effects of caffeine.
咖啡因是一种非选择性腺苷受体拮抗剂，具有促觉醒和促交感神经系统兴奋作用，这些药理作用与食欲素的生理功能非常契合。本研究旨在探讨食欲素能神经系统在咖啡因药理作用中的作用。
通过睡眠剥夺建立腺苷蓄积所致嗜睡动物模型，分别采用旷场实验和胃肠蠕动观察评估咖啡因对模型动物自发活动和交感神经系统的影响，并观察食欲素受体拮抗剂对咖啡因药理作用的干预情况。
睡眠剥夺8小时的小鼠自发活动显著减少，胃肠推进距离显著增加。咖啡因干预后，睡眠剥夺小鼠的自发活动显著增加，胃肠蠕动呈剂量依赖性显著降低，而食欲素受体拮抗剂可阻断咖啡因对睡眠剥夺小鼠的促觉醒和抑制胃肠蠕动作用。
食欲素能神经系统介导了咖啡因对促觉醒和促交感神经系统的兴奋作用。食欲素可能是咖啡因药理作用的重要执行者。
