• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.183-192
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

• Journal of Microbiology and Biotechnology
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• 제21권10호
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• pp.1088-1096
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• 2011

The purpose of this study was to evaluate whether wild ginseng (WG) administration could attenuate anxiety- and depression-like behaviors and expression of corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) following withdrawal from repeated morphine administration in rats. Male rats were administered daily doses of WG (50, 100, or 200 mg/kg, i.p.) for 5 days, 30 min before morphine injection (40 mg/kg, s.c). The anxiety- and depression-like behavioral responses were measured 72 h after the last morphine injection using an elevated plus maze (EPM) and forced swimming test (FST), respectively. Changes in hypothalamic CRF and NPY expressions were also examined by analyzing their immunoreactivities in the hypothalamus. Daily administration of WG significantly reduced anxiety- and depression-like behavior, and elicited the suppression of CRF expression and the stimulation of NPY expression in the hypothalamus. Our results demonstrated that WG extract might be effective at inhibiting the anxiety and depression responses due to morphine withdrawal by possibly modulating the hypothalamus CRF and NPY systems. Furthermore, these findings imply that WG extract can be used for developing new medication to cure or alleviate morphine withdrawal symptoms and to prevent relapses of morphine use.

• 약학회지
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• 제49권4호
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• pp.291-298
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• 2005

Gardenia Jasminoides(GJ) is traditionally used for treatment of hepatic disease, insomnia, anxiety, and inflammatory disease. The aim of this study is to examine effects of GJ extract in response to stress. Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng and GJ supplementary group were orally administered once a day with 100mg of red ginseng extract, 100mg of GJ extract/kg body weight. The mice were given water containing 200mg of red ginseng extract, 200mg of GJ extract/100ml potable water. Animals were given supplements for 7 days without stress, and then were given supplements for 5 days with restraint and electroshock stress. After loading final stress, we examined stress related behavioral changes of experimental animals and measured the levels of blood corticosterone. GJ-supplementation partially blocked the stress effect on locomotion and elevated plus maze test in rats, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, face-washing, smelling and rearing behavior in rats. The effect was almost equipotent to Ginseng's effect. GJ-supplementation didn't influence on fatigue related behavior or physical stress resistance. GJ-supplementation decreased the levels of blood corticosterone which is increased by stress in rats. These results suggest that GJ protects partially the living organism from stress attack and it has the potential to be used as a functional material to alleviate stress response.

• 대한본초학회지
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• 제27권4호
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• pp.81-88
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• 2012

Objective : Banhahubak-tang is indicated for globus hystericus, marked by a subjective sensation as if something stuffed in the throat, chest distress, cough or vomiting, greasy whitish, taut and smooth pulse. In this study, the effects of Banhahubak-Tang extract (BHTe) were tested for anti-stress action. Methods : BHTe was extracted by pure water using electronic extractor and then fed to ICR male mice ($20{\pm}2g$) orally with the dose of 100mg/kg/day for five days. Mice were exposed to sociopsychological stress by restraining and seeing foot shock stressed mice for one hour for five days. Results : BHTe administered group showed a tendency of decreasing of serum corticosterone secretion when compared with control group, and BHTe administration also significantly up-regulated noradrenaline secretions in the dorsal cortex of brain. Lipid peroxidation of the brain tissues of mice were tested by measuring malondialdehyde, but BHTe showed no significant change. The elevated plus-maze test was designed to detect the effect of anxiolytic drugs, and BHTe administered group showed a significant increase of latency time. Conclusions : These results suggest that BHTe can effectively rid the psychological stress and it's related diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.525-538
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

• 동의신경정신과학회지
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• 제18권2호
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• pp.45-55
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• 2007

Objective : The purpose of this study was to investigate the protective effects of Radix Curcumae 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. Radix Curcumae of l00mg/kg administered 4. Radix Curcumae 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, Radix Curcumae of 400mg/kg group showed significantly decreased anxiety. 2) In forced swimming test, Radix Curcumae of 400mg/kg group showed significantly decreased immobilization. 3) In passive avoidance test, stress group showed significantly decreased learning execution, Radix Curcumae groups showed significantly increased learning execution. 4) Stress group showed significantly increase in serum level of corticosterone, Radix Curcumae of 400mg/kg group showed significantly decreased serum level of corticosterone. Conclusion : These results suggest that Radix Curcumae is effective in the treatment of depression.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.83-89
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• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].

• 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.