Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 90, Issue 3, Pages 399-403Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2008.03.022
Keywords
spinosin; hypnotic effect; pentobarbital sleep; semen Zizhiphi Spinozae; serotonergic system
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Semen Zizhiphi Spinozae has been used extensively for the treatment of insomnia. This study investigated the effect and possible mechanism of action of spinosin (also known as 2 ''-beta-o-glucopyranosyl swertisin), a major constituent of semen Zizhiphi Spinozae, on sleep in mice. The present results showed that spinosin significantly and dose-dependently augmented pentobarbital (45 mg/kg, i.p.)-induced sleep, reflected by increased sleep time and reduced sleep latency assessed with the loss-of-righting reflex, and these effects were potentiated by the 5-hydroxytryptamine (serotonin) precursor 5-hydroxytryptophan (5-HTP, 2.5 mg/kg, i.p.). With a subhypnotic dose of pentobarbital (28 mg/kg, i.p.), spinosin significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleep time, and spinosin significantly reversed this effect. The dopamine precursor L-3-(3, 4-dihydroxyphenylalanine (L-DOPA) reduced pentobarbital-induced sleep, an effect not significantly affected by spinosin. These results suggest that spinosin potentiated pentobarbital-induced sleep via a serotonergic mechanism. (C) 2008 Elsevier Inc. All rights reserved.
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