The orexinergic system mediates the excitatory effects of caffeine on the arousal and sympathetic activity
Yan Li,
Zhixuan Guo,
Chenxi Cai,
Danni Liu,
Yin Kang,
Pengfei Liu
Affiliations
Yan Li
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; Corresponding author. 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.
Zhixuan Guo
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
Chenxi Cai
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
Danni Liu
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
Yin Kang
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
Pengfei Liu
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
Objective: 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. Methods: 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. Results: 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. Conclusions: 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.