Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT1A receptors

Wang, L.-E.; Cui, X.-Y.; Cui, S.-Y.; Cao, J.-X.; Zhang, J.; Zhang, Y.-H.; Zhang, Q.-Y.; Bai, Y.-J.; Zhao, Y.-Y.

doi:10.1016/j.phymed.2010.01.014

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Volume 17, Issue 6 , Pages 404-409, May 2010

Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT_1A receptors

L.-E. Wang
- Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China
X.-Y. Cui
- Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China
S.-Y. Cui
- Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China
J.-X. Cao
- Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China
J. Zhang
- Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China
Y.-H. Zhang
- Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China
- Corresponding author. Tel./fax: +861082801112.
Q.-Y. Zhang
- Department of Natural Medicine, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Y.-J. Bai
- Department of Natural Medicine, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Y.-Y. Zhao
- Department of Natural Medicine, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

published online 22 February 2010.

Abstract

Previous results have suggested that spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, potentiates pentobarbital-induced sleep via the serotonergic system. The present study investigated whether spinosin potentiates pentobarbital-induced sleep via serotonin-1A (5-hydroxytryptamine, 5-HT_1A) receptors. The results demonstrated that spinosin significantly augmented pentobarbital (35 mg/kg, i.p.)-induced sleep in rats, reflected by reduced sleep latency and increased total sleep time, non-rapid eye movement (NREM) sleep time, and REM sleep time. With regard to NREM sleep duration, spinosin mainly increased slow-wave sleep (SWS). Additionally, spinosin (15mg/kg, i.g.) significantly antagonized 5-HT_1A agonist 8-OH-DPAT (0.1mg/kg, i.p.)-induced reductions in total sleep time, NREM sleep, REM sleep, and SWS in pentobarbital-treated rats. These results suggest that spinosin may be an antagonist at postsynaptic 5-HT_1A receptors because these effects of 8-OH-DPAT were considered to be mediated via postsynaptic 5-HT_1A receptors. Moreover, co-administration of spinosin and the 5-HT_1A antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylbenzamide (p-MPPI), at doses that are ineffective when administered alone (spinosin 5mg/kg, p-MPPI 1mg/kg), had significant augmentative effects on pentobarbital-induced sleep, reflected by reduced sleep latency and increased total sleep time, NREM sleep, and REM sleep. In contrast to the attenuating effects of p-MPPI on REM sleep via presynaptic 5-HT_1A autoreceptors, 15mg/kg spinosin significantly increased REM sleep. These results suggest that the effect of spinosin on REM sleep in pentobarbital-treated rats may be related to postsynaptic 5-HT_1A receptors.