• 동의생리병리학회지
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• 제24권3호
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• pp.476-483
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• 2010

The present study was performed to investigate the putative anxiolytic-like effects of the aqueous extract of the roots of Scrophularia buergeriana (SB-W) using elevated plus-maze (EPM) and hole-board apparatus in mice. SB-W was orally administered at doses of 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation. Control group were administered with an equal volume of saline, and positive control group with buspirone (2 mg/kg, i.p.). The administration of SB-W significantly increased the percentage of time spent in open arms and entries into the open arms of the EPM compared with saline-treated control group (P < 0.05). Futhermore, those anxiolytic-like activities of SB-W were antagonized by flumazenil (a $GABA_A$ antagonist, 10 mg/kg), but not by WAY-100635 (a 5-$HT_{1A}$ antagonist, 0.3 mg/kg). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with saline-treated control group. In the hole-board test, the administration of SB-W (200 and 400 mg/kg) significantly increased the number of head-dipping compared with saline-treated control group (P < 0.05). Therefore, these findings suggest that Scrophularia buergeriana promotes the anxiolytic-like activity mediated by GABAergic nervous system in mice.

• 동의생리병리학회지
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• 제28권6호
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• pp.614-620
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• 2014

Kainic acid (KA) is a excitatory agonist causing epileptic seizure and excitotoxicity in the hippocampus. Gastrodia Elata (GE) is known to have anti-convulsant and anti-oxidant effects. This study was investigated a possible role of GE in suppressing epileptic seizure using KA-induced epilepsy mouse model. Eight-week-old male C57BL/6 mice were administrated GE (50 or 500 mg/kg) once a day for 5 days, and then injected KA (30 mg/kg) intraperitoneally. Behavioral changes in mice by KA were evaluated for 90 minutes immediately after the KA administration. Six hours after the KA administration, their brains were harvested and the expressions of glutamate decarboxylase 67 (GAD-67) and K+-Cl- cotransporter 2 (KCC2) in the hippocampus of the mice were measured by immunohistochemistry.GE delayed the onset of epileptic seizure after KA administration, suppressed the severity of the seizure and decreased the number of severe seizures dose dependently. Moreover, GAD-67 and KCC2 expressions in the cornu ammonis (CA) 1 and CA3 of 500 mg/kg GE administrated mice were significantly increased compared to those in KA-treated mice.GAD-67 and KCC2 play an important role in regulating GABAergic system. Our results suggest that GE has anti-convulsant effect against KA-induced epileptic seizure through enhancing GABAergic system.

• The Korean Journal of Pain
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• 제11권1호
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• pp.23-29
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• 1998

Background: The present study was conducted to investigate effects of microinjection of bicuculline, GABA-A receptor antagonist, into the brain stem nuclei on the dorsal horn neuron responsiveness in rats with an experimental peripheral neuropathy. Methods: An experimental neuropathy was induced by a unilateral ligation of L5~L6 spinal nerves of rats. After 2~3 weeks after the surgery, single-unit recording was made from wide dynamic range (WDR) neurons in the spinal cord dorsal horn. Results: Responses of WDR neurons to both noxious and innocuous mechanical stimuli applied to the somatic receptive fields were enhanced on the nerve injured side. These enhanced responsiveness of WDR neurons were suppressed by microinjection of bicuculline into periaqueductal gray(PAG) or nucleus reticularis gigantocellularis(Gi). A similar suppression was also observed when morphine was microinjected into PAG or Gi. Suppressive action by Gi-bicuculline was reversed by naloxonazine, ${\mu}$-opioid receptor antagonist, microinjected into PAG whereas PAG-bicuculline induced suppression was not affected by naloxonazine injection into Gi. Gi-bicuculline induced suppression were reversed by a transection of dorsolateral funiculus(DLF) of the spinal cord. Conclusions: The results suggest that endogenous opioids, via acting on GABAergic interneurons in PAG and Gi, may be involved in the control of neuropathic pain by activating the descending inhibitory pathways that project to the spinal dorsal horn through DLF to inhibit the responsiveness of WDR neurons.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.307-312
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• 2022

It is well known that dopamine transmission from the ventral tegmental area (VTA) modulates motivated behavior and reinforcement learning. Although dopaminergic neurons are the major type of VTA neurons, recent studies show that a significant proportion of the VTA contains GABAergic and type 2 vesicular glutamate transporter (VGLUT2)-positive neurons. The non-dopaminergic neurons are also critically involved in regulating motivated behaviors. Some VTA neurons appear to co-release two different types of neurotransmitters. They are VGLUT2-DA neurons, VGLUT2-GABA neurons and GABA-DA neurons. These co-releasing neurons show distinct features compared to the neurons that release a single neurotransmitter. Here, we review how VTA cell populations wire to the other brain regions and how these projections differentially contribute to motivated behavior through the distinct molecular mechanism. We summarize the activities, projections and functions of VTA neurons concerning motivated behavior. This review article discriminates VTA cell populations related to the motivated behavior based on the neurotransmitters they release and extends the classical view of the dopamine-mediated reward system.

• 대한한방내과학회지
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• 제19권1호
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• pp.57-72
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• 1998

This study has been carried out to investigate the effects of Ukgansan(UGS) extract on anti-convulsive, antipyretic, analgesic, sedative and GABAergic system of experimental animals. The results of this study were as follows : 1. UGS extract prolonged significantly the beginning time to convulsion and death induced by strychnine. 2. UGS extract prolonged significantly the time to death induced by electrical shock of ECT unit.(3 sec, 200 F, 25 mA) 3. On the experiment of hypothermic effects of UGS extract on the rectal temperature of mouse, UGS extract decreased significantly the rectal temperature of mouse 4. On the experiment of antipyretic effects of UGS extract on the febrile induced by the subcutaneous injection of $150\;{\mu}g/kg$ endotoxin in mouse, UGS extract decreased significantly the rectal temperature of mouse. 5. On the experiment of analgesic effects of UGS extract on the writhing syndrome induced by intraperitoneal injection 0.7% acetic acid 1 ml/100g in mouse, the writhing syndrome induced by acetic acid was reduced significantly by administration of UGS extract. 6. On the experiment of effects of UGS extract on spontaneous motor activity measured by wheel cage method in mice, the spontaneous motor activity was reduced significantly by administration of UGS extract. 7. On the experiment of effects of UGS extract on the activity of GABA-transaminase(GABA-T) in mouse brains after 21 days of oral administration of UGS extract. the activity of GABA-T was reduced significantly by administration of UGS extract. 8. On the experiment of effects of UGS extract on the activity concentration of GABA in mouse brain after 21 days of oral administration of UGS extract, the activity concentration of GABA was reduced significantly by administration of UGS extract. 9 On the experiment of effect of UGS water extract on the activity of GAD in mouse brain after 21 days of oral administration of UGS extract, the activity of GAD was reduced significantly by administration of UGS extract. According to the these results, Ukgansan extracts reveal the effects on the anti-convulsive, antipyretic, analgesic, sedative and GABAergic system.

• 생명과학회지
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• 제24권3호
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• pp.290-296
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• 2014

이 연구의 목적은 mice를 이용하여 elevated plus-maze (EPM) test와 hole-board test를 통해 quercetin의 잠재적인 항불안 작용을 확인하고자 함이다. Quercetin을 1.25, 2.5, 5나 10 mg/kg의 용량으로 각각 행동시험을 측정하기 1 시간 전에 ICR mice에 경구투여하였다. 대조군은 동일한 양의 10% Tween 80을 투여하였고 양성대조군으로 buspirone 2 mg/kg을 투여하였다. Quercetin을 단회 투여하여 EPM test를 실시한 결과, 5 mg/kg 용량에서 open arm에 머문 시간 및 진입한 횟수의 백분율이 control group과 비교하여 통계적으로 유의성 있게 증가하였다(p<0.05). 또한 quercetin을 투여하여 hole-board test를 실시한 결과, 5 mg/kg 용량에서 구멍에 머리를 넣은 횟수가 control group과 비교하여 통계적으로 유의성 있게 증가하였다(p<0.05). 또한 quercetin와 flumazenil ($GABA_A$ antagonist), WAY-100635 ($GABA_{A-{\rho}}$ antagonist) 또는 trans-4-aminocrotonic acid ($GABA_{A-{\rho}}$ agonist)를 병용투여하여 elevated plus-maze를 실험을 하여 신경계와의 관계를 확인한 결과, trans-4-aminocrotonic acid에서만 quercetin의 항불안 작용이 차단되었음을 확인 할 수 있었다. 결론적으로, 본 연구의 결과에서 quercetin이 elevated plus-maze 및 hole-board test, horizontal wire test, open field test를 통하여 locomotor activity 및 근육이완이나 진정 등의 부작용이 없으면서 우수한 항불안 작용을 가지는 소재라고 생각되며 이러한 작용이 특히 GABA 신경계와 관련이 있음을 시사하고 있다.

• 대한한방내과학회지
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• 제18권2호
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• pp.65-82
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• 1997

This study has been carried out to investigate the effects of Cheonmagudeungyeum(CGY) extract on anti-convulsive, antipyretic, analgesic, sedative and GABAergic system of experimental animals. The results of this study were as follows : 1. CGY extract prolonged significantly the beginning time to convulsion and death induced by strychnine. 2. CGY extract prolonged significantly the time to death induced by electrical shock of ECT unit(3 sec, 200 F, 25 mA) 3. On the experiment of hypothermic effects of CGY extract on the rectal temperature of mice, CGY extract decreased the rectal temperature of mice. 4. On the experiment of antipyretic effects of CGY extract on the febrile induced by the subcutaneous injection of $150\;{\mu}g/kg$ endotoxin in mice, CGY extract decreased significantly the rectal temperature of mice. 5. On the experiment of analgesic effects of CGY extract on the writhing syndrome induced by intraperitoneal injection 0.7% acetic acid 1 ml/100g in mice, the writhing syndrome induced by acetic acid was reduced significantly by administration of CGY extract. 6. On the experiment of effects of CGY extract on spontaneous motor activity measured by wheel cage method in mice, the spontaneous motor activity was reduced significantly by administration of CGY extract 7. On the experiment of effects of CGY extract on the activity of GABA - transaminase (GABA-T) in mouse brains after 21 days of oral administration of CGY extract, the activity of GABA-T was reduced significantly by administration of CGY extract. 8. On the experiment of effects of CGY extract on the activity concentration of GABA in mouse brain after 21 days of oral administration of CGY extract, the activity concentration of GABA was reduced significantly by administration of CGY extract. 9. On the experiment of effect of CGY water extract on the activity of GAD in mouse brain after 21 days of oral administration of CGY extract, the activity of GAD was reduced significantly by administration of CGY extract. According to the these results, Cheonmagudeungyeum extracts reveal the effects on the anti-convulsive, antipyretic, analgesic, sedative and GABAergic system.

• Natural Product Sciences
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• 제26권1호
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• pp.1-9
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• 2020

Flavonoids are mainly contained in the vegetables and medicinal herbs. Until now, over 5,000 kinds of flavonoid have been identified and their biological activities have been reported. Among them, we are interested in oroxylin A and spinosin because of their specific structures having bulky group at C-6 of ring A. Oroxylin A is contained in the Scutellaria baicalensis and exhibits cognitive enhancing activity as a GABA_A receptor antagonist, which is different from those of mainly contained in the S. baicalenis, baicalein or wogonin. Spinosin is isolated from Zizyphus jujuba var. spinosa and mainly studied as a hypnotic or anxiolytic agent because of traditional knowledge about its original herb. As far as we know, the cognitive function of spinosin was first identified by our group. In this review, we discuss how such flavonoids exert their pharmacological activities associated with cognitive function based on the receptor binding study and behavioral studies. Traditional knowledge and reverse pharmacology may be addressed in the research field of phytochemical pharmacology and useful to unveil the secret of phytochemicals.

• 대한약리학회지
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• 제28권1호
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• pp.27-40
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• 1992

Taurine은 유황 함유 아미노산으로서 뇌내에서 억제작용을 갖는 신경전달물질 역할을 하는것으로 알려져 있다. Taurine을 가토의 측뇌실내에 투여하여 혈압 및 심박에 미치는 영향을 검토하고 그 작용 기전을 규명코자 본 연구를 시행하여 얻은 연구결과는 다음과 같다. Taurine $(0.15{\sim}1.5\;mg)$은 urethane 마취 가토의 측뇌실내로 주사하였을때 혈압강하작용 및 심박감소작용이 현저하고 지속적인 용량반응 곡선을 나타내었다. 이와 동시에 상당한 호흡억제 작용도 관찰되었다. 그러나 동일량의 taurine을 정맥내에 투여시 혈압 및 심박에 아무런 영향을 미치지 못하였다. Taurine의 혈압 하강작용은 chlorisondamine, clonidine, strychnine, bicuculline등으로 전처치시 유의하게 억제되었으나 atropine, 양측 미주신경절단, propranolol 및 metoclopramide등의 전처치로 영향을 받지 않았다. 더우기 taurine은 norepinephrine의 승압 반응에도 영향을 미치지 못하였다. Taurine의 심박감소 작용은 chlorisondamine, propranolol, clonidine, strychnine 및 bicuculline등으로 전처리시 현저히 차단되었으나 atropine, 양측 미주신경절단, metoclopramide 등의 전처리로 영향을 받지 않았다. 이상의 연구한 결과로 보아, taurine은 가토의 측뇌실내 투여시 지속적이며 현저한 혈압하강 및 심박감소를 일으키며 이러한 작용은 뇌내의 catecholamine 뉴론과 관련있는 taurine (glycine) 및 gamma-aminobutyric acid (GABA) 수용체를 통해서 나타나는 것으로 사료된다.

• 한국동물학회지
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• 제39권1호
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• pp.1-11
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• 1996

GABA antagonist인 SR 95531이 닭의 pretectum nuclei (nucleus Superficialis Synencephali nSS) 또는 nBOR (nucleus Ectomammilaris nEM)속에 미량 주입되었다. 단안의 optokinetic nystagmus는 한쪽 뇌의 내부에 약품을 주입하기 전후에 탐색 코일 테크닉에 의해서 기록되었다. 한쪽 nSS 또는 nEM 속에 SR 95531를 미량 주입하면 자극의 양방향에 대하여 반대쪽 눈에 의해서 유도된 단안의 OKN속도 게인이 가역적으로 증가하였다. 이때 nSS속에 주입하면 N-T 성분의 속도 게인보다 T-N 성분의 속도 게인을 더욱 강하게 증가시킴으로써 방향적 불균형성이 더욱 증가되었다. 한편 nEM 속에 약품을 주입하게 되면 T-N 성분의 속도 게인보다 N-T 성분의 속조 게인이 더욱 강하게 증가함으로써 방향적 불균형성을 제거했다. 이것으로부터 우리는 nSS 특히 N-T 자극에 방응에 단안의 OKN이 관련되어 있고, nEM은 N-T 자극에 대한 OKN 반응에 더욱 관련되어 있는 것으로 유추할 수 있었다. 이 결과는 그 약품이 중뇌 수준에서 OKN에 관련된 GABAergic 메카니즘의 억제작용을 제거한다는 것을 암시한다. 미량 주입된 핵에 대하여 같은쪽 눈에 의해서 유도된 OKN의 게인의 증가는 수평적 OKN에 관련된 이들 중뇌 구조들 사이에 강한 상호작용이 존재한다는 것으로 설명된다.