• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.427-448
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• 2019

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying $K^+$ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.

• Journal of Acupuncture Research
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• v.26 no.4
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• pp.99-106
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• 2009

Objectives : The antidepressant effect of the subchronic administration of the methanolic extract of wild ginseng(WG) was investigated compared with that of cultivated ginseng(CG, panax ginseng) extract. Methods : To assess the antidepressant effect of the ginseng extracts, tail suspension test(TST) was executed in mice after daily administration of WG or CG extract for five consecutive days. Results : The WG extract at daily dose of 600mg/kg significantly reduced the total duration of immobility in the TST, whereas there was no significant reduction at daily dose of 300mg/kg WG and 600mg/kg CG. There were no individual differences between experimental groups in open field test (OFT) to evaluate psychostimulant effects of WG or CG extract. In the high performance liquid chromatography(HPLC) analysis of the extracts, it was found that WG included four times more ginsenoside Rg1 and Re, three times more Rf, and six times more Rb1 and Rc than CG. Conclusions : It is suggested that WG extract has stronger antidepressant effect than CG extract, which means it includes more antidepressant compounds than CG.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.226-232
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• 2001

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.129-146
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• 2011

Objectives : The purpose of this study was to characterize the putative antidepressant and antianxiolytic effects of the 70% ethanol extract of Polygala japonica(EEPJ) using animal's behavioral experiment in mice. Methods : The effect of EEPJ on the anxioty and depressive disorder was investigated via mice's behavioral experiment like Elevated plus-maze, Horizontal wire test, Open field test, Forced swimming test, Tail suspension test, and it was happen via any mechanism by WAY 100635, a 5-HT1A receptor antagonist and by Flumazenil, a GABAA antagonist Results : 1. In the EPM, single treatments of the EEPJ(200 and 400mg/kg) had usefully antianxiolytic effects versus vehicle, which was medicated via the serotonergic nervous system. 2. In the HWT, single treatments of the EEPJ were no changes in the myorelaxant effects versus vehicle. 3. In the OFT, single treatments of the EEPJ were no changes in the locomotor activity versus vehicle. 4. In the FST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. 5. In the TST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. Conclusions : These results indicate that EEPJ is an effective antidepressant and antianxiolytic activity in mice, and it might be usefully applied for prevention and treatment of depressive disorder through evolutive study like development of various experimental models.

• The Korean Journal of Pain
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• v.20 no.1
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• pp.71-73
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• 2007

Tricyclic antidepressant (TCA) is a useful drug for treating neuropathic pain. However, tremors are one of the relatively frequent side effects of TCA. A female patient, who was suffering from postherpetic neuralgia, was treated with amitriptyline starting with 10 mg/day. She developed resting tremors on the second day after increasing the dose to 30 mg/day. This case highlights the need for the careful use of amitriptyline in the treatment of neuropathic pain in elderly patients.

• Korean Journal of Medicinal Crop Science
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• v.22 no.3
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• pp.196-202
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• 2014

Depression is one of the most common neuropsychiatric disorders and has been associated with the neuroendocrine system and alterations in behavior. Schisandra chinensis Baillon is one of major medicinal plants used as a Korea medicine and food sources, and has been processed in the fields of various food products and medicinal herbs. The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviors in laboratory mice or rat. The CMS procedure induced some behavioral changes that are compatible with the common expectations, i.e. 'anhedonic' behavior and can affect corticosterone level. The present study, Schisandra chinensis extract administration by daily gavage from the 3 weeks exhibited an antidepressant-like effect on CMS-induced depression in mice. Schisandra chinensis extract administration at dose of 200mg/kg significantly increased the sucrose consumption, and decreased the immobility durations in forced swim test and tail suspension test. Furthermore the corticosterone level decreased than control group. In conclusion, Schisandra chinensis extract showed antidepressant-like effects on sucrose preference test, forced swimming test and tail suspension test based on CMS model.

• Journal of Pharmacopuncture
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• v.21 no.1
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• pp.35-40
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• 2018

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

• Biomedical Science Letters
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• v.24 no.3
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• pp.206-212
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• 2018

Depression is a type of mood disorder characterized by hypochondriasis, decreased appetite, and insomnia. Depression is a disease that affects more than 100 million people worldwide. 2-Nonadecanone (NAC) is a bioactive substance that constitutes Fomes fomentarius, and NAC is expected to have an antidepressant effect. By using the forced swimming test (FST), we investigated the effects of treatment with NAC on immobility subacutely in rats after oral dosing once a day for 2 days. Serum levels of cytokine interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-2 (Nrf-2) and inducible nitric oxide synthases (iNOS) were analyzed by western blot method. NAC dose-dependently decreased immobility in the FST. NAC dosedependently decreased FST-induced increase of cytokine levels, as manifested by significantly stronger effects on $IL-1{\beta}$ and $TNF-{\alpha}$ levels at higher doses than the lowest dose of NAC. Western blot analysis showed that Nrf-2 was significantly lower in the NAC-treated group than in the disease-induced group. The iNOS results were also significantly lower in the NAC-treated group than in the other groups. Considering FST results, the antidepressant effect of NAC is effective. Considering the results of cytokine and protein expression, this anti-depressant effect may be related to the anti-inflammatory effect. Therefore, it can be said that the anti-inflammatory effect of NAC increases the antidepressant effect in the FST experiment.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.429-435
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• 2006

The antidepressant effects of Cirsium japonicum compositae was investigated using open field test and forced swimming test. Total extract of Cirsium japonicum (CJ) was orally administered at dose of 20, 100, 300, 500 mg/kg bodyweight. Supplementation of CJ increased dose-dependently movement, rearing frequency and total turn angle in the center area of open field in mice. Treatment of Cirsium japonicum's extract (300 mg/kg, CJ) decreased immobile duration and increased mobile and strong mobile duration significantly; and it is comparable to that of imipramine and fluoxetine. These results indicate that CJ has antidepressant effect. Treatment of CJ did not induced any impairment in motor coordination and myorelaxation. These results indicate that the constituents or its complex of Cirsium japonicum could be a candidate of new antidepressant drug.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.227-239
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• 2023

Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant implications for future research not only with PCP analogs but also on the next generation of different types of antidepressants.