The involvement of serotonin receptors in suanzaorentang-induced sleep alteration

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-HT(2), 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-HT(2) antagonist (ketanserin) or 5-HT(3 )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.