title: 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.
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.
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100191, China.
authors.forename: L-E
authors.initials: LE
authors.lastname: Wang
authors.forename: X-Y
authors.initials: XY
authors.lastname: Cui
authors.forename: S-Y
authors.initials: SY
authors.lastname: Cui
authors.forename: J-X
authors.initials: JX
authors.lastname: Cao
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Zhang
authors.forename: Q-Y
authors.initials: QY
authors.lastname: Zhang
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Bai
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Zhao
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006027:Glycosides; D008297:Male; D009005:Monosaccharides; D010424:Pentobarbital / Q000494:pharmacology; D008517:Phytotherapy; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds; D012701:Serotonin / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy; D012895:Sleep, REM; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects*; D031957:Ziziphus / Q000737:chemistry*
chemical_list: D000631:Aminopyridines; C438934:C-glycoside; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D006027:Glycosides; D009005:Monosaccharides; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D012701:Serotonin; C055669:spinosin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010424:Pentobarbital