• 대한한방부인과학회지
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• 제26권4호
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• pp.14-29
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• 2013

목 적: 본 연구는 갱년기 우울증 모델에서 사물탕가향부자(SGH)의 항우울 효능 및 면역반응에 대한 실험적 유의성을 확인함으로써 임상적인 응용에 기초자료로 사용하기 위하여 시행되었다. SGH가 반복적인 스트레스를 가한 난소적출 흰쥐에서 항우울행동 효과와 estradiol level 및 anti-inflammatory cytokine인 IL-4에 미치는 영향을 연구하고자 하였다. 방 법: 난소적출 흰쥐에 2주간 반복적인 스트레스를 주고 동시에 SGH(200 and 400 mg/kg/day)를 경구 투여한 후 행동검사인 Elevated Plus Maze(EPM)를 통한 우울행동과 혈청 estradiol, IL-4의 변화를 측정하였고, 또한 뇌 내 Locus coeruleus(LC)와 Paraventricular Nucleus(PVN)에서 IL-4의 변화를 측정하였다. 결 과: 1. EPM에서 SGH 400 mg 투여군은 대조군에 비해서 open arms에 머무는 시간이 현저히 증가하였고, closed arms에 머무는 시간이 현저히 감소하였다. 2. EPM에서 SGH 투여군은 대조군에 비해서 open arms와 closed arms를 교차하는 횟수가 증가하였으나, 통계적인 유의성은 없었다. 3. Estradiol 측정에서 SGH를 투여한 후 estradiol 수준이 현저하게 증가하였다. 4. IL-4 측정에서 SGH를 투여한 후 혈청 IL-4 수준이 현저하게 증가하였다. 5. 뇌에서의 IL-4 면역반응은 대조군에서 감소하였으나, SGH를 투여한 후 LC와 PVN에서 IL-4 수준의 유의성 있는 변화는 나타나지 않았다. 결 론: 이상의 결과로 사물탕가향부자는 난소적출 흰쥐의 항우울행동과 면역조절에 유효함을 알 수 있었다.

• 동의신경정신과학회지
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• 제22권2호
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• pp.85-105
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• 2011

Objectives : The purpose of this study was to characterize the neuroprotective effects and anxiolytic-like effects of Gongjin-dan and Polygala japonica, Polygala tenuifolia, Acorus gramineus mixed pills(G.J.D-P.P.A.). Methods : The neuroprotective effects of G.J.D-P.P.A. determined by the passive avoidance and Y-maze tasks and Morris water maze task, and the anxiolytic-like effects of the G.J.D-P.P.A. using an elevated plus-maze(EPM) in mice. Results : Drug-induced amnesia was induced by treating animals with scopolamine(1 mg/kg, i.p.). A single G.J.D-P.P.A.(400 and 800 mg/kg) administration significantly enhanced cognitive function and attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks(P < 0.05) and also reduced escape-latency on the Morris water maze task(P < 0.05). The administration of GJD-PPA(400 and 800 mg/kg) 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). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with saline-treated control group. Conclusions : These results suggest that GJD-PPA dramatically possesses the anti-amnestic and cognitive-enhancing activities related to the memory processes, and promotes the anxiolytic-like activity in mice.

• 한국식품위생안전성학회지
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• 제30권1호
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• pp.120-125
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• 2015

본 연구는 Sprague-Dawley 계통의 4주령 랫드에서 MSG의 반복경구투여 독성평가와 행동실험을 통해 어린랫드의 인지능력과 불안감에 미치는 영향을 평가하기 위해서 시행하였다. 시험군은 MSG 대신 distilled water를 투여한 대조군(Control, n = 4), MSG를 3 g/kg을 투여한 군(Low, n = 4), MSG를 5 g/kg을 투여한 군(High, n = 4)으로 나누어 4주 동안 주5회 경구투여를 하였다. MSG의 안정성을 확인하기 위해 다음과 같은 관찰 및 검사를 하였다. 검사항목으로는 체중의 변화, 임상증상, 행동실험인 T-maze, Elevated-plus-maze와 혈액학적 검사, 혈청생화학적 검사, 병리조직학적 검사를 관찰한 결과 모든 투여군 및 대조군에서 특이할 만한 임상증상과 체중변화는 관찰되지 않았으며, 폐사 및 빈사 동물은 시험 전 기간을 통하여 발견되지 않았다. 행동실험인 T-maze 결과 MSG 고용량 투여군에서 움직이는 횟수가 감소하다 증가하는 양상을 보였고, Elevated-plus-maze 실험에서는 MSG 고용량 투여군의 Open arm의 출입빈도가 증가하는 등 유의적인 변화가 나타났다. 혈액학적 검사 및 혈청생화학적 검사에서는 대조군과 비교 시 유의적인 변화가 관찰되었지만 그 수치가 정상범위 안에 포함되기 때문에 이상을 나타내지 않았다. 병리조직검사 또한 약간의 염증발생 소견이 나왔지만 정상범위 안에 포함되기 때문에 이상을 나타내지 않았다고 판단했다. 따라서, 어린랫드를 이용한 MSG의 반복투여 독성시험 결과 특이할만한 신체적인 변화는 나타나지 않았으나 고용량의 MSG 투여는 어린랫드에서 인지능력의 저하 및 행동의 불안을 유발할 가능성이 있다고 사료된다.

• Advances in Traditional Medicine
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• 제5권4호
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• pp.301-307
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• 2005

The roots of the plant Korean ginseng have been extensively used in the traditional Chinese herbal medicine. We investigated the standardized extract of Korean ginseng on animal models of anxiety based on exploratory behavior. Korean ginseng extract (KGE) (3, 10 and 30 mg/kg) was administered intra-peritoneally. The anxiolytic activity was studied using elevated plus maze (EPM) paradigm, light/dark apparatus (LDA), open field apparatus (OFA) and the hole board apparatus (HBA). Diazepam (1mg/kg) was used as a standard anxiolytic drug. In EPM, KGE (10 mg/kg) significantly (P < 0.05) increased the time spent in open arms and the number of entries in open arms. In LDA, KGE (10 mg/kg) increased the number of transitions. In OFA, KGE (3 and 10 mg/kg) significantly increased (P < 0.05) the number of squares traversed. In HBA the number of head pokes were significantly increased with KGE (3 and 10 mg/kg). KGE at all selected doses did not affect the motor coordination. Thus, the study suggests that saponin containing standardized Korean ginseng extract possess anxiolytic activity.

• 동의신경정신과학회지
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• 제22권2호
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• pp.129-146
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• 2011

Objectives : The purpose of this study was to characterize the putative antidepressant and antianxiolytic effects of the 70% ethanol extract of Polygala japonica(EEPJ) using animal's behavioral experiment in mice. Methods : The effect of EEPJ on the anxioty and depressive disorder was investigated via mice's behavioral experiment like Elevated plus-maze, Horizontal wire test, Open field test, Forced swimming test, Tail suspension test, and it was happen via any mechanism by WAY 100635, a 5-HT1A receptor antagonist and by Flumazenil, a GABAA antagonist Results : 1. In the EPM, single treatments of the EEPJ(200 and 400mg/kg) had usefully antianxiolytic effects versus vehicle, which was medicated via the serotonergic nervous system. 2. In the HWT, single treatments of the EEPJ were no changes in the myorelaxant effects versus vehicle. 3. In the OFT, single treatments of the EEPJ were no changes in the locomotor activity versus vehicle. 4. In the FST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. 5. In the TST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. Conclusions : These results indicate that EEPJ is an effective antidepressant and antianxiolytic activity in mice, and it might be usefully applied for prevention and treatment of depressive disorder through evolutive study like development of various experimental models.

• 대한한방부인과학회지
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• 제26권4호
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• pp.30-47
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• 2013

목 적: 본 연구는 만성 스트레스로 인한 갱년기 우울증 모델에서 사물탕가향부자(SGH)의 항우울 효과를 검증하여 실험적 유의성을 확인하고자 시행되었다. 방 법: 난소적출 흰쥐에 4주간 만성 스트레스를 가하고 SGH(100 and 400 mg/kg/day)를 투여한 후 행동검사인 sucrose intake test(SIT), elevated plus maze(EPM), forced swimming test(FST) 및 Morris water maze test(MWMT) 등을 통한 우울행동 변화와 혈청 corticosterone(CORT), IL-$1{\beta}$ 및 IL-4 등의 변화를 측정하였고, 또한 뇌 내 hippocampus와 hypothalamus에서 5-HT의 변화를 측정하였다. 결 과: 1. SIT에서 SGH 400 mg/kg/day 투여군은 대조군에 비해서 자당 섭취가 유의하게 증가하였다(p<0.05). 2. EPM에서 SGH 400 mg/kg/day 투여군은 대조군에 비해서 open arms에 머무는 시간이 유의하게 증가하였고(p<0.01), open arms와 closed arms를 교차하는 횟수도 대조군에 비해서 유의하게 증가하였다(p<0.05). 3. FST에서 SGH 100 mg/kg/day, 400 mg/kg/day 투여군 모두 대조군에 비해서 immobility시간이 유의하게 줄어들었다(SGH 100 p<0.05, SGH 400 p<0.01). 4. MWMT에서 SGH 100 mg/kg/day, 400 mg/kg/day 투여군은 모두 대조군에 비해서 실험 4일째에서 acquisition trials 수행 시간이 유의하게 단축되었고(p<0.05), SGH 400 mg/kg/day 투여군은 대조군에 비해서 retention trials 수행 시간이 유의하게 증가하였다(p<0.05). 5. CORT와 IL-4 측정에서 대조군과 SGH 투여군 모두 유의한 변화가 없었고, IL-$1{\beta}$ 측정에서 대조군에서는 유의하게 증가하였지만 SGH 투여군에서는 대조군에 비해서 유의한 변화가 없었다. 6. Hippocampus에서의 5-HT 측정에서 SGH 400 mg/kg/day 투여군은 대조군에 비해서 유의하게 증가하였다(p<0.05). Hypothalamus에서의 5-HT수준은 SGH 투여군 모두 대조군에 비해서 유의하게 증가하였다(SGH 100 p<0.05, SGH 400 p<0.01). 결 론: 이상의 결과로 SGH는 만성 스트레스를 가한 난소적출 흰쥐에서 항우울 효과가 있음을 알 수 있었고, HPA axis, immune system 보다 5-HT system에 작용하는 것으로 사료된다.

• The Korean Journal of Pain
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• 제35권1호
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• pp.22-32
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• 2022

Background: Migraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine. Methods: Adult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group): untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals' sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box. Results: We observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat). Conclusions: The findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.191-200
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• 2014

We investigated the anxiolytic-like activity of ${\alpha}$-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

• 동의신경정신과학회지
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• 제19권3호
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• pp.101-115
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• 2008

Objective: The purpose of this study was to investigate the protective effects of Sam-Jeong-Hwan(SJH) on the animal model of depression induced immobilization stress. Method: The subject were divided into 4 groups(l. normal 2. saline solution administered during immobilization stress treatment 3. SJH of 100mg/kg administered 4. BKJ of 400mg/kg administered). Immobilization stress was treated for 1 hours on day. During 2 days of immobilization stress treatment, they were executed forced swimming test, passive avoidance test, elevated plus maze test. Corticosterone and ACTH in blood were measured. Results: In forced swimming test, SJH of 400mg/kg group showed decreased immobilization. In passive avoidance test, SJH of 400mg/kg group showed increased learning execution. In EPM test, SJH of 400mg/kg group showed decreased anxiety. In locomotor activity test, SJH groups showed significantly increased locomotor activity. Stress group showed significantly increase in serum level of corticosterone, SJH of 400mg/kg group showed decreased serum level of corticosterone. Stress group showed significantly increase in serum level of ACTH, SJH of 400mg/kg group showed decreased serum level of ACTH. Conclusion: These results suggest that Sam-Jeong-Hwan(SJH) is effective in the treatment of depression.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.313-322
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• 2013

Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.