The present study was undertaken to elucidate the characteristics of red ginseng total saponin in behavioral changes on ambulation, forced swim test and convulsion in mice. The ambulation and the duration of immobility on forced swim test were not affected by red ginseng total saponin. On the other hand, the duration of immobility inducted by DMI, PGL but not CIP was significantly decreased, and the onset of convulsion induced by pentylenetetrazole was significantly shortened by preadministration of red ginseng total saponin. These results suggest that red ginseng total saponin component may play an important role in modulating synergism with drugs acting on depression and convulsion, and that the characteristics of synergetic effect induced by red ginseng total saponin potentate the central norepinephrine neuron activity.
Objectives : For the purpose of verifying the anti-depressant effect of Paeoniae Radix Rubra(PR), the expression of corticotropin-releasing factor(CRF), c-Fos and tyrosine hydroxylase(TH) was evaluated after performing the Forced Swimming Test(FST). Methods : Spraque-Dawley rats were ingested PR extract(100mg/kg, 400mg/kg, p.o.) for 3 times prior to FST. And the expression of corticotropin-releasing factor(CRF), c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coelureus(LC) and ventral tegmental area(VTA) was measured immunohistochemically after FST. Results : The duration of immobility was significantly decreased in PR 100mg/kg Group and PR 400mg/kg Group, in comparison with the control group (p<0.001). The expression of CRF in the PVN was significantly decreased in PR 400mg/kg Group in comparison of the control group (p<0.05). The expression of c-Fos in the PVN was rather significantly increased in PR 100mg/kg Group in comparison with the control group, while almost no change was demonstrated in PR 400mg/kg Group. The expression of TH was significantly decreased in VTA in comparison with the control group (p<0.05), but the number of expression cells in LC was slightly decreased in case of PR 100mg/kg group while it was increased in case of PR 400mg/kg Group. Conclusion : Judging from the result of the aforementioned tests, Paeoniae Radix Rubra has decreased immobility. In addition, it has also decreased the expression of CRF and the expression of TH in VTA, while the expression of c-Fos and of TH in LC has no significance. Therefore, it is believed that Paeoniae Radix Rubra has an anti-depressant effect by decreased immobility through the reduced expression of CRF and TH in VTA.
Park, Soo-Jin;Choi, Min-Ji;Chung, Sun-Yong;Kim, Jong-Woo;Cho, Seung-Hun
Journal of Oriental Neuropsychiatry
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v.24
no.3
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pp.271-280
/
2013
Objectives : The development of natural drugs with antidepressant effects is important and needed. This study was performed to investigate the antidepressant-like effects of the distilled water extract of Portulaca oleracea L. (POL) in a mouse model and to investigate the role of ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in producing these antidepressant-like effects. Methods : The forced swim test (FST) and tail suspension test (TST) were used to investigate the behavioral anti-depressive-like effects of POL in mice. Additional behavioral experiments with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione, an AMPA receptor antagonist, were undertaken to determine the involvement of the antidepressant-like properties of POL in AMPA receptor throughput. Results : Oral administration of the POL extract (100 mg/kg) 1 h prior to testing significantly reduced the immobility times in the FST and TST. The antidepressant-like effects of the POL extract were not increased in a dose-dependent manner. Pre-treatment with NBQX significantly attenuated the reduction in immobility time induced by the POL extract in the FST. Conclusions : The distilled water extract of POL has antidepressant-like effects, which may be related to AMPA receptor. Pre-treatment with NBQX significantly attenuates the reduction in immobility time induced by the POL extract in the FST.
Journal of the Korea Academia-Industrial cooperation Society
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v.15
no.11
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pp.6739-6745
/
2014
Acer tegmentosum Maxim (AT) is a species of the maple genus, which is native to North-Eastern China and Korea. Traditionally, AT has been already used for pain relief in Korea. On the other hand, its antidepressant-like activity and related molecular mechanisms is not completely understood. Using the Forced Swimming Test (FST), the effects of a subacute treatment with AT(100, 200, and 400 mg/kg, p.o.) on the immobility and FST-induced changes to the immune parameters, cortisol, ACTH, and cytokine, in rats were investigated. The tendency of immobility showed a dose-dependent decrease in FST. The levels of cortisol, IL-6 and $IL-1{\beta}$ in the peripheral blood were increased significantly after FST exposure. Overall, these results suggest that AT treatment can decrease the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of AT might be involved in the antidepressant-like effect.
The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-${\alpha}$ levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to $17{\alpha}$-ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-${\alpha}$ along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by $17{\alpha}$-ethinylestradiol $30{\mu}g/kg/day$ for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-${\alpha}$ and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and $17{\alpha}$-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-${\alpha}$ and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-${\alpha}$ might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-${\alpha}$ and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.
Objectives : The effect of mixture extracted from Bupleuri Radix and Physalidis Herba(BR+RH) on the LPS-induced Depression in rats was investigated. Methods : Rats were administered intragastrically BR+PH after injectio of LPS to induce deprssion. Immobility was examined using Tail Suspension Test(TST), Forced Swimming Test(FST). The level of plasma corticosterone was measured by an Enzyme-Linked Immunosorbent Assay(ELISA) method. The expressions of c-Fos, Corticotropin Releasing Factor(CRF), NADPH-d in the Paraventricular nucleus(PVN) and TH in the Locus coeruleus(LC) were measured by immunohistochemical method. Results : In the effect of BR + PH on TST, immobility was significantly decreased comparing with the LPS group. In FST, immobility was shown decrease tendency in the BR+PH group. The expression of c-Fos in the PVN was significantly decreased at BR + PH400 group, comparing with the LPS group. The expression of CRF in PVN was shown dto have the decrease tendency in the BR+PH group, comparing with the LPS group. The expression of NADPH-d in PVN was not significantly decreased at BR+PH groups, comparing with the LPS group. The expression of TH in the LC was shown to have the decrease tendency at BR + RH groups, but not significantly, comparing with the LPS group. Conclusions : Anti-depressant effect of mixture after extracted from Bupleuri Radix and Physalidis Herba was through the anti-inflammatory effect via inhibition of HPA axis. NO and catecholamine system is not involved.
Kim, Yunna;Lee, Hwa-Young;Choi, Yu-Jin;Cho, Seung-Hun
Journal of Ginseng Research
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v.44
no.4
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pp.603-610
/
2020
Background: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alphaaminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. Methods: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. Results: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. Conclusion: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.
Choi, Hyung Jun;Im, Soo Jung;Park, Hae Ri;Lee, Seong Mi;Kim, Chul-Eung;Ryu, Seunghyong
Korean Journal of Biological Psychiatry
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v.27
no.1
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pp.27-35
/
2020
Objectives Ketamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigate the behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. Methods In each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly divided into 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive 3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT) and forced swim test (FST), respectively. Results In case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman's rho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobility in the FST (Spearman's rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher compared to the saline-treated mice (Dunnett's post-hoc test, p = 0.012). Conclusions We found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobility in mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.
Objectives : Investigation of the antidepressant effect of Glycyrrhizae Radix (GR) through the anti-inflammatory effect. Methods : Depression in rats was induced by LPS (i,p.3days). The rats were treated with GR100 mg/kg (GR 100) or GR400 mg/kg (GR 400). The depressive immobility was examined with Tail Suspension Test(TST) and Forced Swimming Test(FST). The expression of nuclear factor-${\kappa}B$(NF-${\kappa}B)$, $I{\kappa}B$ was measured with western blotting. The concentration of corticosterone, cytokine in plasma was measured with ELISA. The expression of c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coeluleus(LC) were measured with immunostaining method. Results : In the TST, GR400 group significantly decreased immobility time compared with the LPS group. In the FST, GR100, GR400 group significantly decreased immobility time comparing with the LPS group. c-Fos expression in GR100 and GR400 group was decreased comparing with the lipoplysaccharide(LPS) group. The $I{\kappa}B$ expression of GR100 and GR400 group was increased comparing with the LPS group. The level of corticosterone of GR100 group was decreased comparing with the LPS group. The concentration of cytokine of GR100 and GR400 group was decreased comparing with the LPS group. TH expression in the LC was increased in LPS group, but in GR100 and GR400 group was not shown significant decrease. Conclusion : According to this results obtained, GR has antidepressant effects by the anti inflammatory action through the suppression of HPA axis activity, not through the action against the catecholaminergic system.
1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.
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