• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.27-36
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• 2017

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of $GABA_A$-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and $0.1{\mu}g/ml$) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of $GABA_A$-ergic systems, and can be useful in the treatment of insomnia.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.586-592
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• 2017

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via ${\gamma}$-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through $GABA_A$-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.179-194
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• 1995

This study aimed to determine whether exposure to stress during developmental period causes permanent behavioral and/or neurochemical alterations. Alterations of behavior were studied in young and aged rats which have been exposed to uncontrollable and unpredictable electric shocks on postnatal day(PND) 14 or PND 14 and 21. The concentrations of monoaminergic neurotransmitters were also measured to determine whether the behavioral alterations were accompanied by neurochemical changes. The results obtained are as follows: 1) The rate of increase in body weight was reduced at one day after exposure to the 1st series of shocks on PND14. However, these findings could not be observed after exposure to the 2nd series of shocks on PND 21. 2) Explorative activity decreased at one day after exposure to the 1st series of shocks on PND14. However this findings could not be observed after exposure to the 2nd series of shocks on PND 21. 3) At 100 days of age, there were little changes in the spontaneous locomotor activities measured for consecutive 23 hrs. However, there was positive correlation between the shock number showing the 1st helplessness during receiving the 1st series of shocks and the night time ambulatory activity of females, and was negative correlation between the shock number showing the 1st helplessness during receiving the 1st or 2nd series of shocks on PND 14 or 21 and the night time ambulatory activity of females. 4) At $360{\sim}390$ days of age, night time ambulatory activity decreased in female rats which have been exposed to shocks on PND 14 and 21, but not in males. 5) In the aged female rats, the concentrations of 5-HT, dopamine and their metabolites were not different among groups. However, the ratio of 5-HIAA/5-HT increased in the frontal cortices of rats exposed to shocks on PND 14 and 21. These results demonstrate that the early experience of serious stress results in persistent alterations of behavior accompanying altered neurochemistry, and aging may unmask a subtle neuronal deficit causes by the early experience of serious stress.