• 생약학회지
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• 제42권1호
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• pp.32-37
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• 2011

The effects of herbal ethanol extract from Gynostemma pentaphyllum (GP extract) on chronic stress-induced anxiety in mice were investigated. The animals were treated with GP extracts (50 and 100 mg/kg/day, p.o.) for 21 days before exposure to electric footshock (EF; duration and interval 10 sec for 3 min, 2 mA) for chronic stress once a day. The ambulatory locomotor activity was reduced by chronic EF stress and it was recovered by 12.9-15.1% in GP extract-treated groups. The grip strength was also significantly decreased by chronic EF stress, however, the EF-stressed groups treated with GP extract increased grip strength from 13.9% to 56.8% compared to EF-stressed groups. In addition, the serum levels of corticosterone were significantly elevated by chronic EF stress to 197% of the control levels, which was reduced to 73.1% by treatment with GP extract (100 mg/kg). In contrast, the brain levels of dopamine and serotonin were reduced to 67.6% and 63.1% by chronic EF stress, which was recovered to 90% of the control levels by treatment with GP extract. These results indicate that GP extract shows the ameliorating effects on chronic EF stress-induced anxiety in mice and it can be developed as the promising anti-anxiety agent.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.263-268
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• 2014

The etiology of most psychiatric disorders is still incompletely understood. However, growing evidence suggests that stress is a potent environmental risk factor for depression and anxiety. In rodents, various stress paradigms have been developed, but psychosocial stress paradigms have received more attention than non-social stress paradigms because psychosocial stress is more prevalent in humans. Interestingly, some recent studies suggest that chronic psychosocial stress and social isolation affects mainly anxiety-related behaviors in mice. However, it is unclear whether chronic non-social stress induces both depression- and anxiety-related phenotypes or induces one specific phenotype in mice. In the present study, we examined the behavioral consequences of three chronic non-social stress paradigms: chronic predictable (restraint) stress (CPS), chronic unpredictable stress (CUS), and repeated corticosterone-HBC complex injection (RCI). Each of the three paradigms induced mild to severe depression/despair-like behaviors in mice and resulted in increased immobility in a tail suspension test. However, anxiety-related phenotypes, thigmotaxis and explorative behaviors, were not changed by the three paradigms. These results suggest that depression- and anxiety-related phenotypes can be dissociated in mouse stress models and that social and non-social stressors might affect brain circuits and behaviors differently.

• Journal of Ginseng Research
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• 제45권2호
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• pp.254-263
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• 2021

Background: A chronic social defeat stress (CSDS) model has been proposed as relevant to stress-induced behavioral change in humans. In this study, we examined the effect of Korean Red Ginseng (KRG) on CSDS-induced mood disorders and protein expression in an animal model. Methods: To evaluate the effect of KRG on social defeat stress, test mice were exposed in the resident aggressor's home cage compartment for 14 days beginning 1 h after KRG treatment (10, 20, and 40 mg/kg, per oral (p.o.)). After the exposure, behavioral tests to measure anxiety, social interaction, and depression-like behavior were performed. To investigate the underlying mechanism, N-methyl-D-aspartate receptor expression levels in CSDS-induced mice were evaluated using Western blot analysis. Results: CSDS induced anxiety-like behaviors by decreasing central activity in the open-field test and open-arm approach in the elevated plus maze test and led to social avoidance behavior in the social interaction test. CSDS mice showed upregulated NR1, NR2A, and NR2B expression in the hippocampus. KRG 20 and 40 mg/kg ameliorated anxiety-like activities and KRG 20 mg/kg alleviated social avoidance by decreasing time in the corner zone. KRG treatment recovered CSDS-induced NR1, NR2A, and NR2B protein levels in the hippocampus. Conclusion: These results indicate that KRG has a therapeutic effect on CSDS-induced mood disorder by alleviating N-methyl-D-aspartate receptor overexpression in the hippocampus.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.523-528
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• 1997

Peripheral benzodiazepine receptor(PBR) has been indentified in various peripheral tissues including kidney. The physiological and pharmacological functions of PBR are still uncertain, althought it has been suggested that these are associated with the regulation of stress/anxiety response. Diazepam progeny, which were exposed to diazepam perinatally, was reported to be an animal model of chronic anxiety. However, PBR in the diazepam progenies are not known yet. In the present study, therefore, we examined the changes of PBR in the stress/anxiety response. Dams of rats were given injection of diazepam or vehicle during puerperium. Diazepam progenies showed increased level of anxiety on the performance of elevated plus maze, and increased Bmax of PBR. Saturation experiments followed by scatchard analysis of the results showed that the increase in the density of PBR and the affinity of the PBR remained unchanged. Forced swim stress increased anxiety on the plus maze in both groups of rats. In contrast to control, diazepam progenies did not show further upregulation of renal PBR immediately after swimming stress, but still higher than control. From the above results, it may be concluded that upregulation of renal PBR is associated with chronic anxiety as well as stress-induced response.

• 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.

• 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.

• Natural Product Sciences
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• 제15권4호
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• pp.213-221
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• 2009

Longanae Arillus (the rind of fruits of Dimocarpus longan) has been consumed for the treatment of insomnia and anxiety in Asia. To provide further scientific basis to traditional uses of this fruit on insomnia, we evaluated the effects of methanol extract of Longanae Arillus (MELA) on the alteration of sleep architecture and electroencephalogram (EEG) power spectra in acutely and chronically restraint-stressed rats. Following postsurgical recovery, Polygraphic signs of sleep-wake activities were recorded for 24 h after MELA administration in rats. Rats in the acute stress and chronic stress were administered with MELA for 10 days. On the $8^{th},\;9^{th}\;and\;10^{th}$ day of MELA administration, the rats were stressed for 3 h once per day. On the $10^{th}$ day and 1 h after MELA administration, the rats were stressed once for 22 h in the chronic stress group. Acute and chronic stress induced alternations in cortex EEG recordings during non-rapid eye movement (NREM), rapid eye movement (REM) sleep and wakefulness. MELA shortened the total and REM sleep and increased the wakefulness in night time recording without changing daytime recordings. Chronic stress increased wakefulness and REM sleep, decreased total and NREM sleep in the daytime recording, and increased REM and decreased NREM sleep without changing total sleep and wakefulness in night time recording. These findings suggest that MELA ameliorated the alterations in REM and NREM sleep of acutely and chronically stressed rats via modulation of cortical ${\alpha}-$, ${\theta}-$ and ${\delta}-$ wave activity.

• 동의신경정신과학회지
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• 제14권2호
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• pp.61-78
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• 2003

Objective : This study was designed to assess the protective effects of Chengwhabosimtang on the animal model of depression, chronic mild stress(CMS). Method : Male Sprague-Dawley rats were used for this experiment. The subjects were divided into 3 groups ( 1. CMS-drug: Chengwhabosimtang administered during CMS treatment, 2. CMS-vehicle: water administered, 3. normal ). After 4 weeks of CMS treatment, they were executed Forced swimming test(FST) and Elevated plus maze. Tyrosine hydroxylase(TH) in ventral tegmental area(VTA) and c-Fos in paraventricular nucleus(PVN) were measured. Result : 1. In FST, CMS-drug group showed significantly decreased immobility behavior. 2. CMS-drug group showed no significantly lower TH level in VTA than CMS-vehicle group. 3. CMS-drug group showed significantly less c-Fos expressed cell bodies in PVN than CMS-vehicle group. 4. In Elevated plus maze, CMS-drug group showed no significantly anxiety. Conclusion : These results suggest that Chengwhabosimtang may have protective antidepressant effects in CMS model rats. And these effects could be explained by the elevated stress-copying behaviors which are related with PVN of hypothalamus and dopaminergic neurons in VTA.

• 동의신경정신과학회지
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• 제30권3호
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• pp.209-220
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• 2019

Objectives: As a general emotion, everyone can temporarily experience depression, but depressive disorder is a disease that excessively affects daily life. Among the various causes of depression, the deficiency of monoamine-based neurotransmitters such as serotonin and epinephrine are considered significant. Thus, antidepressants that target monoamines are used frequently. However, side effects such as nausea, vomiting, insomnia, anxiety, and sexual dysfunction are observed. Thus, it is necessary to develop a new therapeutic agent with fewer side effects. In this study, we investigated the antidepressant effect of JG02, used to treat depression by normalizing the flow of qi (氣) in Korean medicine. Methods: C57BL/6 mice were selected and randomly divided into six groups: normal, control, amitriptyline, and JG02 (50, 125, 250 mg/kg), respectively. Except for normal, depression was induced by applying restraint stress at the same time for six hours daily for 14 consecutive days. Saline, amitriptyline or JG02 samples were orally administered two hours before applying the stress. After that, a forced swimming test and an open field test were performed. Additionally, serum corticosterone, serotonin mRNA, BDNF mRNA, and protein in the hippocampal region were measured and compared. Results: JG02 decreased immobility time rate in the FST and increased the zone transition number and travel distance in the OFT. Also, JG02 inhibited the release of serum corticosterone, and increased serotonin, BDNF gene expression, and BDNF protein in the hippocampus. Conclusions: In this study, JG02 showed significant antidepressant effects on the chronic restraint stress mice model. When further research is performed based on JG02, the development of a new antidepressant is considered highly possible.