Sedative and hypnotic effects of Vaccinium bracteatum Thunb. through the regulation of serotonegic and GABAA-ergic systems: Involvement of 5-HT1A receptor agonistic activity - 09/12/18
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Abstract |
The present study was conducted to investigate the sedative and hypnotic activities of Vaccinium bracteatum Thunb. fruit (VBFW) in an animal model and to identify the underlying mechanisms of its action.
VBFW exhibited sedative effects through a reduction in the locomotor activity in the open field test (OFT). In addition, VBFW significantly reduced the sleep latency and increased total sleep duration in pentobarbital-induced sleeping behaviors in mice. The effects of 4-Chloro-DL-phenylalanine methyl ester hydrochloride (PCPA) were studied in normal and serotonin-depleted mice. Additionally, the changes in the related serum corticosterone (CORT) and neurotransmitter levels were evaluated. Pretreatment with VBFW (50, and 100 mg/kg) produced a significant decrease in the immobility time in the forced swim test (FST), while VBFW 100 plus PCPA treatment attenuated the change in immobility time observed following administration of VBFW alone. However, VBFW plus PCPA treatments did not significantly influence the changes in the locomotor activity that were induced by VBFW alone. The results suggest that VBFW leads to a decrease in the levels of serum CORT and norepinephrine in the hippocampus (HC) region (P < 0.01). Furthermore, PCPA treatment alone decreased serotonin (5-HT) levels in the HC (P < 0.05) and the prefrontal cortex (PFC; P < 0.05), while VBFW plus PCPA significantly increased the 5-HT levels in both the HC and the PFC (P < 0.05). In addition, we also found that VBFW showed a strong agonistic effect at the 5-HT1A receptor by activating 5-HT1A receptor-mediated intracellular Ca2+ and ERK1/2 phosphorylation. Similarly, VBFW (30 and 100 μg/mL) significantly increased the intracellular Cl− influx through its effects on the γ-aminobutyric acid type A receptor (GABAA receptor) subunits (α5, β1, and β2) in primary rat cerebellar granule cells. Moreover, the glutamate decarboxylase (GAD)65/67 protein was upregulated following VBFW treatment (30 and 100 μg/mL). The results of our study indicate that VBFW induces sedative and hypnotic effects by regulating the serotonergic and GABAA-ergic systems, which is possibly associated with 5-HT1A receptor agonistic activity. Additionally, this data suggests that VBFW up-regulates intracellular Cl− and GABAA receptor subunits as well as GAD65/67 protein levels.
Le texte complet de cet article est disponible en PDF.Abbreviations : ANOVA, Akt, BCA, BSA, [Ca2+]i, Cl−, CNS, CORT, CRS, DA, DNase I, ELISA, ERKs, FBS, FST, GABA, GAD, GPCR, HBSS, HC, HRP, IACUC, i.p., MQAE, NE, OFT, 8−OH-DPAT, PBS, PCPA, p-ERK1/2, PFC, PVDF, rpm, RPMI, SEM, 5-HT, s.c., TBS, TMB, VBFW
Keywords : Vaccinium bracteatum Thunb, Insomnia, γ-Aminobutyric acid type A receptors, Glutamic acid decarboxylase, Serotonin 1A receptor
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Vol 109
P. 2218-2227 - janvier 2019 Retour au numéro
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