Abstract
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.
Footnotes
- Received August 13, 2015.
- Accepted October 14, 2015.
C.-R.C. and Y.S. contributed equally to this work.
This work was supported in part by grants-in-aid for scientific research from the National Natural Science Foundation of China (81420108015, 81301135, 31171010, 31171049, 31121061, 31271164, J1210041, 31471064, 31421091,81420108015, 31530035), the National Basic Research Program of China (2015CB856401, 2011CB711000), a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005), the Shanghai Committee of Science and Technology (13ZR1403200, 14JC1400900, 13dz2260700, 13140903100), and the Shanghai Leading Academic Discipline Project (B119).
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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