PT  - JOURNAL ARTICLE
AU  - Chang-Rui Chen
AU  - Yu Sun
AU  - Yan-Jia Luo
AU  - Xin Zhao
AU  - Jiang-Fan Chen
AU  - Yuchio Yanagawa
AU  - Wei-Min Qu
AU  - Zhi-Li Huang
TI  - Paeoniflorin Promotes Non-rapid Eye Movement Sleep via Adenosine A<sub>1</sub> Receptors
AID  - 10.1124/jpet.115.227819
DP  - 2016 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 64--73
VI  - 356
IP  - 1
4099  - http://jpet.aspetjournals.org/content/356/1/64.short
4100  - http://jpet.aspetjournals.org/content/356/1/64.full
SO  - J Pharmacol Exp Ther2016 Jan 01; 356
AB  - Paeoniflorin (PF, C23H28O11), one of the principal active ingredients of Paeonia Radix, exerts depressant effects on the central nervous system. We determined whether PF could modulate sleep behaviors and the mechanisms involved. Electroencephalogram and electromyogram recordings in mice showed that intraperitoneal PF administered at a dose of 25 or 50 mg/kg significantly shortened the sleep latency and increased the amount of non-rapid eye movement (NREM). Immunohistochemical study revealed that PF decreased c-fos expression in the histaminergic tuberomammillary nucleus (TMN). The sleep-promoting effects and changes in c-fos induced by PF were reversed by 8-cyclopentyl-1,3-dimethylxanthine (CPT), an adenosine A1 receptor antagonist, and PF-induced sleep was not observed in adenosine A1 receptor knockout mice. Whole-cell patch clamping in mouse brain slices showed that PF significantly decreased the firing frequency of histaminergic neurons in TMN, which could be completely blocked by CPT. These results indicate that PF increased NREM sleep by inhibiting the histaminergic system via A1 receptors.