• The Korean Journal of Pain
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• v.35 no.1
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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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• v.18 no.3
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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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• v.11 no.4
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• pp.249-256
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• 2003

Pyroligneous liquid(PL) is produced by carbonizing Oak in 350-40$0^{\circ}C$. It is traditionally used for treating stress-related disorder, hepatic disease, immune disorder, G-I disorder and inflammatory disease. The aim of this study is to investigate anti-stress effects of PL. The experiments were performed with the use of young(9 weeks of age) male rats of SD strain and the male ICR mice (20-25 g). Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng, diazepam(BZ) and PL supplementary group were orally administered once a day 100 g of Ginseng extract-kg body weight, 5 mg of BZ/kg body weight and 1 ml of PL100 g body weight and then exposed to stress. The mice of the Ginseng, BZ and PL supplementary group were given water containing 100 g of Ginseng extract/100 ml potable water, 5 mg of BZ/kg 100 ml of drinking water and 10 ml of PL/100 ml of drinking water and exposed to stress. Animals were given materials for 7 days after stabilizing them, and then were given supplementary materials for 5 days with stress. They were stressed by immobilization for 30 minutes and then the animals were exposed to electroshocks for 5 minutes. We recorded stress-related behavioral changes of experimental animals by stressing them using the Etho-vision system and measured the levels of corticosterone in blood While stress suppressed locomotor activity of animals, PL-supplementation partially blocked the stress effect of locomotion in rats and mice, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, smelling and rearing activity in rats and freezing, grooming, tailing and rearing in mice. The staying time of stressed rats and mice in open area decreased and in closed area it increased relatively in elevated plus maze test. However, these changes also partially were blocked by PL-supplementation. PL-supplementation decreased levels of blood corticosterone increased by stress in rats. These results suggest that PL protects partially the living organism from stress attack in some cases.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.20-26
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• 1999

Purpose : Several modulatory factors for renal peripheral benzodiazepine receptor (PBR) has been reported, but their physiological significance remains elusive. Tissue-specific, stress-induced down-regulation of renal PBR coupled with the pharmacological stimulation of these effects by angiotensin II suggested that physiological significance of renal PBR may be related to the pathophysiology of stress-induced hypertension. The boderline hypertensive rat (BHR) has been used extensively to study the interaction of environmental factors, such as stress and blood pressure. The BHR is the first-generation progeny of a cross between the spontaneously hypertensive rat and the control Wistar-Kyoto rat. The pathogenesis of stress induced hypertension in this model is not demonstrated well. Methods In this study, BHR (male, 150-200 g) and Sprague-Dawley (SD, male, 150-200 g) rats were treated by repeated immobilization to induce anxiety. We used plus-maze performance to observe the level of anxiety by measuring percent open crosses and percent time in open. Results : Percent open crosses and percent time in open in BHR were lower than in SD rats (P<0.05). Receptor densities of renal PBR in BHRs were significantly lower than those of SDs (P<0.05). We also observed that the renal PBR was upregulated in the repeatedly stressed (immobilization, 2 hours daily, for 2 weeks) rats, both in the BHR and SD. However, the density of renal PBR in the stressed BHR was still lower than that of stressed SD. Renal PBR has been suggested to be an important organs which Is responsible for the production of cholesterol-derived products during stress. Conrlusion : From these results, it can be summarized that the lowed density of renal PBR may be involved in the pathogeneis of stress-induced hypertension.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.118-125
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• 2008

Gardenia jasminoides (G. jasminoides) is traditionally used to treat insomnia, jaundice, emotional disorders, hepatic disease, and inflammatory disease. Previously, we found that geniposide and the water extract of G. jasminoides increased $Cl^-$ influx in neuroblastoma. Here we examined the sychopharmacological activities of G. jasminoides and its constituents. G. jasminoides extract was orally administered at 100 and 200 mg/kg, and genipin and geniposide were intraperitoneally injected at 2, 10, and 20 mg/kg. G. jasminoides extract (200 mg/kg) significantly decreased total open field activity but increased rearing activity in the center of the open field, suggesting an increase in exploratory activity. Genipin and geniposide did not change open field activity, but geniposide (20 mg/kg) increased rearing activity in the central area. The extract (200 mg/kg) significantly decreased rotarod and wire-balancing activity, but genipin and geniposide did not. No compounds influenced thiopental-induced sleeping or electroshock-induced seizures. The extract (200 mg/kg) significantly increased staying time in the open arms of the elevated plus maze and the entry ratio into the open arms, and geniposide (20 mg/kg) also increased open arm entry. Electroshock stress decreased open arm activity, but the extract and geniposide (20 mg/kg) significantly reversed that effect. This results indicate that G. jasminoides extract and geniposide alleviated anxiety with greater efficacy in stressed animals than normal animals.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.242-249
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• 2004

The main aim of this study was to investigate stress related activities of Sun-ginseng extract as a candidate for anti-stress-related functional supplement by comparing its effect to those of red ginseng, which is also known to alleviate stress. Normal group was not exposed to stress while the control group was exposed to stress. Rats were orally administered once a day with 200 mg red ginseng (RG) extract, 100 or 200 mg Sun-ginseng (SG) extract/kg body weight. Mice were given water containing 400 mg red ginseng extract, 200 or 400 mg SG/100 mL potable water. Rats were given supplements for 5 days without stress, and 5 days with restraint and electroshock stress. After final stress, stress-related behavioral changes of experimental animals were recorded and levels of blood corticosterone were measured. Mice were given supplements for 5 days through drinking water, and then fatigue related motor activity were recorded. SG-supplementation partially blocked stress effect on locomotion and elevated plus maze test in rats, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, smelling, facewashing, grooming and rearing behavior in rats. SG-supplementation decreased blood corticosterone level which is increased by stress in rats. Effects of SG may not be modulated by GABAnergic nervous system. SG-supplementation prolonged swimming time and staying time on the wire and rotarod wheel in mice. These results suggest that SG partially protects living organisms from stress attack in some cases and thus has the potential to be used as a functional food to alleviate stress response.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.165-173
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• 2005

The main aim of this study was to investigate stress related activities of ginsenosides and their action mechanism. Control group and ginsenoside supplemented groups were exposed to stress while no-stress group was not done. Animals of each group (n=$8\~10$) were orally administerd 100 mg red ginseng extract (R-G), or 10 mg ginsenosides/kg body weight once a day. Animals were given materials for 5 days without stress, and then were given supplements for 5 days with restraint and electroshock stress. Mice were given materials for 5 days for experiments on anti-fatigue effect. After loading final stress, stress-related behavioral changes of experimental animals were examined and plasma corticosterone levels were measured. R-G and ginsenoside $Rb_{1}$ supplementation partially blocked the stress effects on locomotion and elevated plus-maze test in rats and mice. They also partially blocked stress induced behavioral changes such as freezing, smelling, face-washing, rearing behavior in rats. R-G and $Rb_{1}$ decrease adrenal gland size and plasma corticosterone level, which were increased by stress in rats. R-G increased enduring time on the Rota rod, cold water and horizontal wire, but $Rb_{1}$ didn't. Effects of $Rb_{1}$ on plusmaze test were inhibited by administration of flumazenil. These results suggest that $Rb_{1}$ is the main antistress principle in ginseng and it's effect is modulated by GABAnergic nervous system.

• Journal of Oriental Neuropsychiatry
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• v.18 no.1
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• pp.1-14
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• 2007

Objective : The purpose of this study was to investigate the protective effects of Cheongsimondam-tang(COT) on the animal model of depression induced immobilization stress. Method 1) Male rats were used for this experiment. The subject were divided into 4 groups(1. normal 2. saline solution administered during immobilization stress treatment 3. COT of 100mg/kg administered 4. COT of 400mg/kg administered). 2) 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 in blood were measured Results 1) In EPM test, stress group showed significantly increased anxiety, COT groups showed significantly decreased anxiety. 2) In forced swimming test, COT groups did not show significantly decreased immobilization. 3) In passive avoidance test, stress group showed significantly decreased learning execution, COT groups showed significantly increased learning execution. 4) Stress group showed significantly increase in serum level of corticosterone, COT of 400mg/kg group showed significantly decreased serum level of corticosterone. Conclusion : These results suggest that Cheongsimondam-tang(COT) is effective in the treatment of depression.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.27-33
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• 2007

The psychopharmacological profile of ginsenosides has not yet been confirmed systematically although various neuropharmacological activities associated with them have been investigated. In the present study, the psychological activities of Rb1 were investigated to evaluate whether it can be used in treatment or prevention of psychological disorders. Rb1 was intravenously injected at doses of O.2,2,5 and 10 mg/kg. The effects of Rb1 on the $Cl^-$ ion influx were investigated using IMR-32 human neuroblastoma cells. Moreover, locomotor activity, forced swimming activity, activity on rotating rod and activity in elevated plus-maze were tested in mice. Rb1 increased the $Cl^-$ influx into the intracell region in a dose-dependent manner. Rb1 did not cause change in behavior in total open field when locomotor activity was tested, however it increased activities, especially, such as rearing frequency in center area. Administration of Rb1 at 0.2 mg/kg significantly reduced activities on rotating rod however administration at high dosages had no effect on them. Rb1 administration decreased animal immobile time in a water chamber in a dose dependent manner, and increased the strong mobile time of animals. In conclusion, the present results demonstrate that Rb1 contributes to the psychopharmacological effects of ginseng and may be used in treatment or prevention of psychological disorders such as anxiety or depression.

• Journal of Oriental Neuropsychiatry
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• v.25 no.3
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• pp.297-310
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• 2014

Objectives: This study is designed to investigate the effects of Banhahubak-Tang Extract (BHTe) on stress. Methos: BHTe was fed to ICR male mice ($20{\pm}2g$) orally with the dose of 100 mg/kg/day for five days. Mice were then exposed to sociopsychological stress by observing foot shock stressed mice for one hour for five days while restrained. Results: 1) The BHTe-administered group showed a tendency of decreasing of serum corticosterone secretion compared with the control group. 2) The BHTe-administered group showed an increase in noradrenalin secretions in the dorsal cortex of the brain, but it was not significant. 3) BHTe administration had no effect on the brain level of lipid peroxidation. 4) BHTe administration decreased the serum level of lipid peroxidation. 5) BHTe administration decreased the Cu,Zn-SOD in the brain. 6) BHTe administration had no effect on catalase activity in the brain. 7) BHTe administration had no effect on the brain level of GSH. 8) BHTe administration increased the serum level of DPPH free radical scavenging activity, but not significantly enough to make a comparison with BHT. 9) The elevated plus-maze test is designed to detect the effect of anxiolytic drugs. The BHTe group showed a significant increase in latency time. Conclusions: These results suggest that BHTe can effectively rid the subject of the effects of sociopsychological stress.