• 수면정신생리
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• 제7권1호
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• pp.10-17
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• 2000

To investigate the neurobiological bases of learning and memory is one of the ambitious goals of modern neuroscience. The progress in this field of recent years has not only brought us closer to understanding the molecular mechanism underlying long-lasting changes in synaptic strength, but it has also provided further evidence that these mechanisms are required for memory formation. Since twenty years ago, several studies for the tests of the hypothesis that NMDA-dependent hippocampal long-term potentiation(LTP) underlies learning have been reported. Also, in the recent year, data from mutant mice showed that a potential role for NMDA-dependent LTP in hippocampal CA1 and spatial learning. Although the current evidence for the role of NMDA receptor in learning and memory is not still obvious, NMDA receptor seems to act as a critical switch for activation of a cascade of events that underlie synaptic plasticity.

• 대한약리학회지
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• 제10권1호
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• pp.61-65
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• 1974

Berberis koreana Palibin belonging to Berberidaceae family, a common herb in Korea, has been contained some quantity of Berberine analogue and other ingredients. Authors therefore paid attention to its pharmacological actions and examined the effects on sleep duration and rectal temperature in mouse with crystal (A) from Berberis koreana Palibin in Korean native plans. The experiment searching for the effect on sleep duration was performed with pretreatment of Berberis Koreana Palibin crystal (A) 30 min before the administration of 25 % ethanol, and its crystal were also administered intraperitoneally with the intention to examine the effect on rectal temperature in mouse. The results of the experiment were as follows; 1. Crystal (A) from Berberis koreana Palibin was made by extraction with ethanol and HCI. 2. Crystal (A) enhanced the hypnotic activity of alcohol in concentratins of 0.1 mg/10g or 0.15 mg/10g. 3. Rectal temperatures in mice were significantly reduced with administration of crystal (A) in concentrations of 0.1 mg/10g or 0.15 mg/10g. 4. The maximal reduction of rectal temperature and potentiation of the hypnotic activity were observed at 30 min after its administration. From the above results, it is clear that crystal (A) from Berberis koreana Palibin exerts the potentiation of hypnotic action of alcohol and reduction of rectal temperature in normal mouse. Its pharmacological effects are probably derived from the action upon the central nervous system.

• 수면정신생리
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• 제3권1호
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• pp.15-24
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• 1996

REM 수면이 학습 및 기억 과정에 관련이 있다는 증거는 많으나 아직도 향후 밝혀져야 할 부분이 많다. 학습후에는 REM 수면이 유의하게 증가한다는 주장과 증가하지 않는다는 연구결과가 있어 의견의 일치를 보이지 않고 있다. 그러나 연구 결과들을 종합하면 내용이 쉽고 단순한 학습후에는 REM 수면의 증가가 없으나 내용이 복잡하고 생소하며 정서적으로 중요한 학습후에는 유의한 REM 수면의 증가를 보인다는 점에서는 일치하고 있다. 이 결과는 Rotenberg(6)의 학습에 대한 두가지의 서로 상반된 행동양식, 즉 탐색활동과 탐색의 포기라는 관점에서의 해석과 일치한다. 아무튼 REM 수면은 장기 기억의 고정과 유지에 중요하며, 불완전한 학습은 REM 수면의 증가를 자극하는 일련의 사건들은 가동시키고 이는 학습을 완성하는데 기여하는 것으로 보인다. 학습전, 후의 REM 수면의 박탈에 대한 연구도 REM 수면이 학습/기억 과정과 밀접히 관련됨을 시사한다. 학습전 REM 수면의 박탈에 대한 연구는 REM 수면이 장기기억에서 저장의 고정과정에 적극적으로 관여됨을 시사한다. 학습후 REM 수면의 박탈에 대한 연구는 REM 수면 "window"라는 개념을 이끌어 냈고 "window"에 해당하는 시간에 REM 수면을 박탈하면 학습장애를 초래하는데, 특히 학습 후 첫번째 나타나는 REM 수면 "window"가 학습과정에서 가장 중요함을 시사한다. REM 수면의 발생과 관련된 뇌의 전기신경생화학적인 일련의 사건들이 기억과 관련된다는 증거들이 많다. REM 수면중 발생하는 해마의 리듬과 기억의 신경생물 학적 기전에 관한 모델중 대표적인 모델인 장기증폭(long-term potentiation)의 관련성이 제안되고 있으며 REM 수면의 박탈은 중추신경계에서 단백질 합성의 장애 및 acetylcholine과 catecholamine 등의 신경 전달물질의 활성에 장애를 주고 이는 기억장애의 결과로 나타난다는 연구들이 있다. 아직도 REM 수면의 기억관련 기능은 의문점이 많다. 향후 분자생물학의 응용 및 뇌의 대사활동이 수면주기에 따라 아주 다름을 보여주는 brain metabolic mapping technique의 이용은 단백질의 합성의 수준에서 REM 수면과 기억/학습과정의 관련성에 대한 이해를 높여줄 것이다.

• 수면정신생리
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• 제6권1호
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• pp.19-25
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• 1999

Sleep alters both breathing pattern and the ventilatory responses to external stimuli. These changes during sleep permit the development or aggravation of sleep-related hypoxemia in patients with respiratory disease and contribute to the pathogenesis of apneas in patients with the sleep apnea syndrome. Fundamental effects of sleep on the ventilatory control system are 1) removal of wakefulness input to the upper airway leading to the increase in upper airway resistance, 2) loss of wakefulness drive to the respiratory pump, 3) compromise of protective respiratory reflexes, and 4) additional sleep-induced compromise of ventilatory control initiated by reduced functional residual capacity on supine position assumed in sleep, decreased $CO_2$ production during sleep, and increased cerebral blood flow in especially rapid eye movement(REM) sleep. These effects resulted in periodic breathing during unsteady non-rapid eye movement(NREM) sleep even in normal subjects, regular but low ventilation during steady NREM sleep, and irregular breathing during REM sleep. Sleep-induced breathing instabilities are divided due primarily to transient increase in upper airway resistance and those that involve overshoots and undershoots in neural feedback mechanisms regulating the timing and/or amplitude of respiratory output. Following ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include 1) hypocapnia, 2) inhibitory effect from lung stretch, 3) baroreceptor stimulation, 4) upper airway mechanoreceptor reflexes, 5) central depression by hypoxia, and 6) central system inertia. While the respiratory control system functions well during wakefulness, the control of breathing is commonly disrupted during sleep. These changes in respiratory control resulting in breathing instability during sleep are related with the pathophysiologic mechanisms of obstructive and/or central apnea, and have the therapeutic implications for nocturnal hypoventilation in patients with chronic obstructive pulmonary disease or alveolar hypoventilation syndrome.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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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.

• Archives of Pharmacal Research
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• 제27권12호
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• pp.1194-1201
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• 2004

Michael addition of certain nucleophiles on ${\alpha}$ , ${\beta}$-unsaturated ketones 1 led to the formation of adducts 2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds 9 and 11. Also, dialkylmalonates were treated with ${\alpha}$-cyano cinnamide to afford 13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce 15-17. Selected compounds (13 and 6) were screened for muscle relaxant, anticonvulsant, and sedative activities using established pharmacological models. Their activities were compared with that of phenobarbital sodium taken as standard. Compound 6 was the most potent muscle relaxant while compounds 13a and 13c offered the highest anticonvulsant activity. Meanwhile compound 13c showed the highest potentiation of phenobarbital induced sleep in mice.

• 생약학회지
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• 제24권3호
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• pp.231-234
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• 1993

Neuropharmacological profile of Humulus lupulus (hop) extract was studied in mice. At doses above 100 mg/kg(i.p.), it decreased spontaneous locomotor activity and raised the nociceptive threshold in the hot-plate test. At doses above 250 mg/kg (i.p.), it increased pentobarbital-induced sleeping time and produced muscle relaxant effect. At the dose of 500 mg/kg, anticonvulsive effect against pentylenetetrazole-induced convulsion and hypothermic effect was observed.

• 동의신경정신과학회지
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• 제13권2호
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• pp.195-211
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• 2002

Gagamguibitang, a composite Korean medicinal drug prescribed by us, was evaluated for its sedative effects by measurements of potentiation on pentobarbital-induced sleeping time, anticonvulsive activities in animal model, inhibitory effect on GABA transaminase activity, and antioxidative activities in vitro- and/or in vivo assay. The results were summerized as follows : 1. Gagamguibitang showed about 2-fold prolongation of pentobarbital-induced sleeping time compared to the control group after administration(p.o) with 2.0g/kg of mice body weight. 2. Gagamguibitang strongly lengthened onset time of pentylenetetrazole-induced convulsion, shortened the duration of convulsion and diminished the lethality after treatment(p.o) with 1.0g/kg of mice body weight. 3. Gagamguibitang inhibited dose-dependently the brain GABA transaminase activity in vitro compared to the control group and in vivo compared to the pentylenetetrazole-treated group. 4. Gagamguibitang inhibited effectively brain lipid peroxidation by 45.8% at a dose of l0mg/ml in vitro and by 47.5% after oral treatment with 0.5g/kg of mice body weight in vivo assay. 5. Gagamguibitang exhibited a potent scavenging activity on DPPH radical in a dose-dependent manner with ca. 92% activity at l0mg/ml. As a result, Gagamguibitang can be useful for the effective sedative drug in clinical application.