The Involvement of Serotonin Receptors in Suanzaorentang-Induced Sleep Alteration

 

Pei-Lu Yi, Chun-Pang Lin, Chon-Haw Tsai, Jaung-Geng Lin & Fang-Chia Chang

 

Abstract

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Sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are usually prescribed for the insomniac patients; however, the addiction, dependence and adverse effects of those medications have drawn much attention. In contrast, suanzaorentang, a traditional Chinese herb remedy, has been efficiently used for insomnia relief in China, although its mechanism remains unclear. This study was designed to further elucidate the underlying mechanism of suanzaorentang on sleep regulation. One ingredient of suanzaorentang, zizyphi spinosi semen, exhibits binding affinity for serotonin (5-hydroxytryptamine, 5-HT) receptors, 5-HT_1A and 5-HT₂, and for GABA receptors. Our previous results have implicated that GABA_A receptors, but not GABA_B, mediate suanzaorentang-induced sleep alteration. In current study we further elucidated the involvement of serotonin. We found that high dose of suanzaorentang (4 g/kg/2 ml) significantly increased non-rapid eye movement sleep (NREMS) when comparing to that obtained after administering starch placebo, although placebo at dose of 4 g/kg also enhanced NREMS comparing with that obtained from baseline recording. Rapid eye movement sleep (REMS) was not altered. Administration of either 5-HT_1A antagonist (NAN-190), 5-HT₂ antagonist (ketanserin) or 5-HT₃ antagonist (3-(4-Allylpiperazin-1-yl)-2-quinoxalinecarbonitrile) blocked suanzaorentang-induced NREMS increase. These results implicate the hypnotic effect of suanzaorentang and its effects may be mediated through serotonergic activation, in addition to GABAergic system.

 

Key words: suanzaorentang, non-rapid eye movement sleep (NREMS), rapid eye movement sleep (REMS), serotonin

1. Introduction
2. Methods
   1. Pharmacological agents: The Chinese herb mixture suanzaorentang, comprising zizyphi spinosi semen, poria cocos, ligusticum wallichii, anemarrhenae rhizoma and glycyrrhizae in ratio of 4:2:2:2:1, and the placebo starch were manufactured and provided by the Sun-Ten Pharmaceutical Co., Ltd (Taipei, Taiwan).
   2. Animals
   3. Apparatus and recording
   4. Experimental protocol
   5. Statistical analyses
3. Results
   1. Effects of oral administration of starch and suanzaorentang on sleep-wake activity
   2. Effects of 5-HT_1A and 5-HT₂ receptor antagonists, NAN-190 and ketanserin, on suanzaorentang-induced sleep alteration
   3. Effects of 5-HT₃ receptor antagonists, 3-(4-Allylpiperazin-1-yl)-2-quinoxalinecarbonitrile, on suanzaorentang-induced sleep alteration
4. Discussion
5. Reference

 

 

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