• 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 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.

• Journal of Microbiology and Biotechnology
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• 제22권5호
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• pp.708-720
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• 2012

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stress-induced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced open-arm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.113-125
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• 2023

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.213-222
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• 2014

Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitaryadrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.

• Journal of Microbiology and Biotechnology
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• 제22권3호
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• pp.422-430
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• 2012

Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxiety-like behaviors and alters the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamic-pituitary-adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.357-366
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• 2016

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open field after SPS. IBU administration significantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These findings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.418-424
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• 2012

Repeated stress induces corticosterone release. However, it is not clear that stress results in further elevation of corticosterone levels, and the roles of released corticosterone to aggravate stress-related symptoms are also not clear. This study investigated whether neuronal modulation was induced in the amygdala after two kinds of stress, that is, such as electric shock and corticosterone injection. It was found that stress by electric shock decreased the expression of tyrosine hydoroxylase (TH) in the amygdala while the expression of pERK was increased. However, there is no difference in the expressions of TH and pERK in the frontal cortex compared with those of the control group. The level of corticosterone was significantly increased in the serum after stress. To determine the effect of corticosterone on the induction of anxiety and the expression of TH, the rats received corticosterone (20 mg or 40 mg/kg i.p.) for 1 day, 1 week, 2 weeks and 3 weeks, respectively. The spent time in open arms of the EPM (elevated plus maze) test was significantly decreased after 1 week, 2 weeks and 3 weeks. The time spent in open arms of the EPM test after repeated injections of corticosterone was significantly decreased in a dose-dependent manner. The expression of TH in the amygdala was reduced after following repeated corticosterone treatment for 2 weeks and 3 weeks. Collectively, this study suggests that corticosterone has a major role in the induction of anxiety and the modulation of TH expression, at least, in the amygdala.