Current Rapid-Onset Antidepressants and Related Animal Models

2018 ◽  
Vol 24 (22) ◽  
pp. 2564-2572 ◽  
Author(s):  
Kuo Yan ◽  
Yi-Bing Chen ◽  
Jia-Rong Wu ◽  
Kuang-Dai Li ◽  
Yuan-Lu Cui
Keyword(s):  
Mental Disease ◽  
Methodological Approach ◽  
Mammalian Target Of Rapamycin ◽  
Antidepressant Drugs ◽  
Tail Suspension Test ◽  
Rapid Onset ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Gamma Aminobutyric Acid ◽  
Treatment Of Depression

Depression is a common mental disease, and it is one of the most crippling diseases in the world. Although current pharmacotherapies contribute to the treatment of depression, the high incidence of a partial responses or no responses, and delayed onset of the antidepressants, make many patients to experience unsatisfactory results from treatment. In view of the high suicide rate during the period of drug onset, it is critical to find antidepressant drugs with rapid onset for the treatment of depression. This paper mainly reviews some drugs that have rapid antidepressant effect and their mechanisms, including monoaminergic receptor drugs, glutamate receptor drugs, mammalian target of rapamycin (mTOR) signaling agonist, gamma-aminobutyric acid energy (GABAergic) agonist and drug combinations. In addition, we introduce several rodent models currently used to assess antidepressant onset in this review: chronic unpredictable mild stress (CUMS), forced swimming test (FST) and tail suspension test (TST), olfactory bulbectomy (OBX) and other models, which provide a methodological approach for assessing the rapid onset of antidepressant drugs.

scholarly journals Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Lanying Liu ◽  
Zhilu Zou ◽  
Jiangwei Yang ◽  
Xiaoqi Li ◽  
Boran Zhu ◽  
...  
Keyword(s):  
Serum Level ◽  
Gut Microbiota ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Gamma Aminobutyric Acid ◽  
Object Recognition Test ◽  
Microbial Distribution

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut–brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice.Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting.Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice.Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.

scholarly journals 2,3,5,4′-Tetrahydroxystilbene-2-O-beta-D-glucoside Reverses Stress-Induced Depression via Inflammatory and Oxidative Stress Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Cheng-Yong Jiang ◽  
Xiao-Yan Qin ◽  
Mi-Mi Yuan ◽  
Gui-Jiang Lu ◽  
Yong Cheng
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Inflammatory Responses ◽  
Mental Disease ◽  
Chinese Herb ◽  
Antidepressant Drugs ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Polygonum Multiflorum ◽  
And Oxidative Stress

Major depressive disorder (MDD) is a chronic mental disease that adversely affects human mood and cognition. Many first-line antidepressant drugs have high rates of partial responsiveness or nonresponsiveness with side effects, and finding more effective drugs for the treatment of depression is therefore urgently needed. THSG, a main active compound of the traditional Chinese herb Polygonum multiflorum, reportedly acts as a neuroprotective agent. This study aimed to illustrate whether THSG prevents depressive-like behaviors induced by chronic restraint stress (CRS) in an MDD mouse model. Our results demonstrated that the peripheral administration of different THSG doses (10 mg/kg, 20 mg/kg, and 40 mg/kg) reversed the depressive-like behaviors in CRS mice as measured by the tail suspension test, forced swimming test, and open-field test. Further analyses suggested that THSG treatment reduced oxidative stress in both the central and peripheral nervous systems of CRS mice. In addition, heightened inflammatory responses, demonstrated by the increased expression of proinflammatory factors (TNF-α, IL-1β, and IL-6), in hippocampal and prefrontal cortex tissues of CRS mice were inhibited by THSG administration. THSG also restored the diminished Akt signaling pathway in the brains of CRS mice. Moreover, our data suggest increased astrocyte proliferation and neurogenesis in the hippocampus of CRS mice after THSG treatment. Taken together, our results demonstrated an antidepressant effect of THSG in a mouse model of MDD for the first time, and oxidative stress and inflammatory pathways were determined to play roles in this effect.

scholarly journals White Ginseng Ameliorates Depressive Behavior and Increases Hippocampal 5-HT Level in the Stressed Ovariectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Daehyuk Jang ◽  
Hyun-ju Lee ◽  
Kyungjun Lee ◽  
Kyu-Ri Kim ◽  
Ran Won ◽  
...  
Keyword(s):  
Antidepressant Drugs ◽  
Tail Suspension Test ◽  
Ovariectomized Rats ◽  
Antidepressant Effect ◽  
Saline Control ◽  
Stressful Situation ◽  
Sprague Dawley ◽  
Immobility Time ◽  
White Ginseng ◽  
Menopausal Depression

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.

scholarly journals Anti-Depressant Activity of the Leaves of Zanthoxylum Armatum on Swiss Albino Mice

2020 ◽  
Vol 8 (02) ◽  
pp. 46-50
Author(s):  
Chandrajeet Kumar Yadav ◽  
Kamal Poudel ◽  
Roshan Mehta ◽  
Amit Kumar Shrivastava
Keyword(s):  
Methanolic Extract ◽  
Forced Swim Test ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Medical Problem ◽  
Mild Stress ◽  
Swiss Albino Mice ◽  
Zanthoxylum Armatum ◽  
Albino Mice

INTRODUCTION Depression is a global mental disorder that has high incidence, high recurrence, and high self-mutilation and suicide rates. Although the antidepressant drugs are available for the treatment, depression still continues to be a major medical problem. The present study was designed to study the anti-depressant activity of the leaves extract of Zanthoxylum armatum using forced swim test and tail suspension test (TST) on Swiss albino mice. MATERIAL AND METHODS The anti-depressant activity of the leaves of Zanthoxylum armatum was assessed using chronic unpredictable mild-stress (CUMS) induced depression in mice. The animals were treated with the methanolic extract of leaves of Zanthoxylum armatum orally at two doses of 100, 200 mg/kg body weight for eight days after (CUMS) induced depression in mice. RESULTS The data were analyzed by one-way ANOVA followed by tukey multiple comparison test. The leaves extract presented significant antidepressant activity in mice (p<0.05), CONCLUSION The results demonstrate that methanolic extract of leaves of Zanthoxylum armatum has got significant antidepressant activity.

scholarly journals Evaluation of the Antidepressant Effect of the Functional Beverage Containing Active Peptides, Menthol and Eleutherosides, and Investigation of Its Mechanism of Action in Mice

2020 ◽  
Vol 58 (3) ◽  
pp. 295-302
Author(s):  
Yuanjin Qi ◽  
Huizhen Zhang ◽  
Sha Liang ◽  
Jiajia Chen ◽  
Xiaoni Yan ◽  
...  
Keyword(s):  
Acute Stress ◽  
Stress Test ◽  
Bovine Milk ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Acanthopanax Senticosus ◽  
Bioactive Substances ◽  
Active Peptides ◽  
Immobility Time

SUMMARY Research background. Depression has become a global threat to human health. In order to solve it, researchers have conducted multi-faceted studies including diet. Many food-derived bioactive substances have shown antidepressant effects. However, there are few studies on the design of industrialized food with antidepressant effect. This study aimed to evaluate the antidepressant effect of a functional beverage made from several ingredients with potential antidepressant function and investigate its antidepressant mechanisms. Experimental approach. The beverage consists of peppermint oil, active peptides derived from bovine milk casein and Acanthopanax senticosus extract (ASE) whose active ingredient is eleutheroside. Different amounts of ASE were evaluated to determine the optimal concentration of eleutheroside in this functional beverage to deliver best antidepressant effect through extensive behavioral testing including preliminary acute stress experiments and further chronic unpredictable mild stress test. Results and conclusions. The results demonstrated that the beverage with 15.00 mg/kg of eleutheroside could significantly reduce the mice’s immobility time of tail suspension test and forced swimming test, recover mice’s sucrose preference and behavior changes in the open-field test, improve the contents of dopamine, norepinephrine, 5-hydroxytryptamine and the activity of superoxide dismutase and reduce the content of malondialdehyde in mice’s brains, which indicated that the improvement of monoamine neurotransmitter systems and antioxidation was one potential mechanism of antidepressant action. Novelty and scientific contribution. This study provides a design of antidepressant functional beverage and an efficient way for the prevention and treatment of depression.

scholarly journals Antidepressant-Like Effect of Geniposide in Mice Exposed to a Chronic Mild Stress Involves the microRNA-298-5p-Mediated Nox1

2021 ◽  
Vol 13 ◽  
Author(s):  
Tianyu Zou ◽  
Jielin Zhang ◽  
Yongxiu Liu ◽  
Yiming Zhang ◽  
Kazuo Sugimoto ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Common Mental Disorder ◽  
Tail Suspension Test ◽  
Luciferase Reporter ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Luciferase Reporter Gene ◽  
Neuroprotective Effects ◽  
Immobility Time ◽  
Gene Assay

Depression is a common mental disorder that presents a considerable challenge for public health. The natural product geniposide has neuroprotective effects on depression, but the underlying mechanism behind these effects had remained undefined. The present study was designed to investigate the role of microRNAs (miRs) in this mechanism. It studied mice with depression-like behavior established by exposure to chronic unpredictable mild stress (CUMS) for 2 months. The CUMS mice were intragastrically fed with geniposide at a dose of 10 ml/kg daily for two consecutive weeks. We monitored the depression-like behaviors of the CUMS mice by the forced swimming test (FST) and tail suspension test (TST). Then, we measured the cerebral expression of miR-298-5p and NADPH oxidase 1 (Nox1) mRNA in the CUMS mice by the RT-qPCR. The targeting relationship between miR-298-5p and Nox1 was evaluated by dual-luciferase reporter gene assay. The concentrations of adenosine triphosphate (ATP) and reactive oxygen species (ROS) were determined by the CellTiter-Glo® and flow cytometry, respectively. The mitochondrial membrane potential (MMP) was detected using JC-1 staining. Moreover, the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and TGF-β) was determined by ELISA, RT-qPCR, and western blot analysis. We found that miR-298-5p was poorly-expressed while Nox1 was highly-expressed in the brain tissues of the CUMS-induced mice. Intriguingly, Geniposide treatment reversed the behavioral abnormalities of CUMS mice, including shortened immobility time. Geniposide inhibited the Nox1 expression by increasing miR-298-5p levels. There were increased ATP content and MMP and reduced contents of ROS and inflammatory cytokines in the CUMS mice receiving geniposide treatment. Hence, this study revealed an antidepressant effect of geniposide on CUMS-induced depression-like behavior in mice by down-regulating the miR-298-5p-targeted Nox1. This highlights a novel candidate target for the treatment of depression.

scholarly journals Beneficial Effects of Crocin against Depression via Pituitary Adenylate Cyclase-Activating Polypeptide

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Linyu Lu ◽  
Die Wu ◽  
Kai Wang ◽  
Juanjuan Tang ◽  
Gang Chen
Keyword(s):  
Adenylate Cyclase ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Pituitary Adenylate Cyclase

Depression is one of the foremost psychological illness, and the exact mechanism is unclear. Recent studies have reported that the pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathway is involved in the progression of depression. In the present study, we extracted crocin from the traditional Chinese medicine (TCM), Gardenia jasminoides Ellis, to evaluate its antidepressant effect and clarify the underlying mechanism. Here, we established a chronic unpredictable mild stress (CUMS) mouse model to assess whether crocin can improve depression-like behavior in an open field test (OFT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT). A corticosterone (CORT) model of PC12 was set up to explore the antidepressant mechanism of crocin. We pretreated PC12 cells with crocin for 1 hour and then stimulated the cells with CORT for 24 hours. Cell survival was detected by Hoechst staining and MTT assay. The expression of PACAP, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and extracellular regulated protein kinases (ERK) were analyzed by western blotting. PACAP RNAi was used to interfere with PC12 cells to downregulate the content of PACAP. The results showed that crocin (30 mg/kg) significantly reversed the decrease of body weight and elevation of serum CORT, mitigated CUMS induced depression-like behaviors of mice, and crocin (12.5 μmol/L) protected PC12 cells against CORT (200 μmol/L)-induced injury. Furthermore, crocin greatly increased the protein expression of PACAP and phosphorylation of ERK and CREB in the CORT model. PACAP RNAi cancelled the neuroprotective effect of crocin. In conclusion, these results indicated that crocin exerted an antidepressant effect via upregulating PACAP and its downstream ERK and CREB signaling pathways.

scholarly journals Antidepressant like activity of Buspirone but not ondensetron in combination with Fluoxetine or Desipramine in mice

2021 ◽  
Vol 10 (6) ◽  
pp. 621
Author(s):  
Veena Verma ◽  
Biswadeep Banerjee ◽  
Ashish K. Mehta
Keyword(s):  
Gradual Increase ◽  
Chronic Mild Stress ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Control Group ◽  
Mild Stress ◽  
Sucrose Consumption ◽  
Immobility Time ◽  
Immobility Period

Background: The involvement of one or more 5-HT receptor sub-types in the pathophysiology of depression is still unclear. The study was performed to investigate the effect of ondansetron and buspirone on depression, and their interaction with fluoxetine or desipramine.Methods: The mice were administered ondansetron, buspirone alone and in combinations with fluoxetine or desipramine for 21 days, and the antidepressant effect was assessed by the immobility period and the sucrose consumption, on the tail suspension test (TST) and the chronic mild stress (CMS) models, respectively.Results: Both ondansetron and buspirone when given alone demonstrated slight non-significant decrease in the immobility time. Ondensetron when given in combination with fluoxetine (10 mg/kg; i.p.) and desipramine (15 mg/kg; i.p.), showed significant decrease in immobility time in comparison to the control group only. On the other hand, both the combinations of buspirone, either with fluoxetine or desipramine showed significant decrease in the immobility time when compared to the respective group. In CMS, the fluoxetine, desipramine, ondansetron, and buspirone showed gradual increase in the sucrose consumption, at the end of 4th, 5th, and 6th week, but the significant effect was observed only at the end of 6th week, as compared to the control. The combination of buspirone with desipramine but not with fluoxetine showed significant increase in sucrose consumption when compared to respective group.Conclusions: Therefore, the study indicates that both buspirone and ondansetron have a potential antidepressant like action, although buspirone has shown better antidepressant activity than ondansetron as observed in various combination groups.

scholarly journals Effects of Baicalin on the ATP Levels in the Prefrontal Cortex in Mice Exposed to Chronic Unpredictable Mild Stress

2021 ◽  
Author(s):  
Shuai-fei Lu ◽  
Xiao-hui Jin ◽  
Lei-lei Zhu ◽  
Ji-duo Shen ◽  
Ming Bai ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mitochondrial Function ◽  
Mental Disease ◽  
Sirtuin 1 ◽  
Antidepressant Effect ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Mice Model ◽  
Peroxisome Proliferator Activated Receptor

Abstract Depression is gradually becoming a primary mental disease threatening human health. It is urgent to clarify the pathogenesis of depression and find new effective natural antidepressants. This study aimed to investigate the antidepressant effects of baicalin and explore its potential mechanism in a mice model of depression induced by chronic unpredictable mild stress (CUMS). Following a 6-weeks CUMS exposure, the CUMS mice were treated with baicalin (10 mg/kg) and fluoxetine (20 mg/kg) for 4 weeks by oral gavage. The sucrose preference test (SPT) and forced swimming test (FST) were performed to evaluate the depression-like behaviors, and the levels of adenosine triphosphate (ATP) in the prefrontal cortex were detected. Moreover, the gene expression and enzyme activities related to the production of ATP and mitochondrial function were detected. The results indicated that the depression-like behaviors of mice induced by CUMS were improved by baicalin and fluoxetine. In addition, baicalin significantly increased the ATP content, the mRNA expression of hexokinase (HK), pyruvate dehydrogenase alpha (PDHα), isocitrate dehydrogenase (IDH), peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC1α), and sirtuin 1 (SIRT1) in the prefrontal cortex. Furthermore, baicalin also increased the activity of respiratory chain complex I, V, and the level of mitochondrial membrane potential (MMP). In conclusion, the present results suggested that the antidepressant effect of baicalin may be partly mediated by accelerating the process of glycolysis and tricarboxylic acid (TCA) and improving the mitochondrial function to enhance the ATP level in the brain.

Comparing onset of effect of antidepressants: Pragmatic considerations on methods and end-points

1998 ◽  
Vol 13 (3) ◽  
pp. 117-123 ◽  
Author(s):  
D Hackett
Keyword(s):  
Methodological Approach ◽  
Antidepressant Drugs ◽  
Antidepressant Effect ◽  
Similar Time ◽  
Time Period ◽  
Research Questions ◽  
Methodological Approaches ◽  
Definition Of ◽  
Study Designs ◽  
Made In

SummaryThere is no accepted definition of what constitutes onset of antidepressant effect, and this limits evaluation of the validity of many comparative reports. In order to clarify the nature of the comparative methodology required, it is proposed that two distinct research questions are separated conceptually: 1) when do antidepressant drugs begin to clinically act? and 2) do all antidepressant drugs produce relief of symptoms in patients within a similar time period? A methodological distinction may also be made in terms of whether to assess the onset of effect of an antidepressant as having an absolute quality (“fast”) or as being fast relative to other treatments (“faster”). The choice of aim will help to define the methodological approach, the applicability of the findings and the difficulties to be addressed. Describing an antidepressant as showing a “fast” or “faster” onset of response requires that any description attempts to define (in terms that may be generalised) the nature of the comparison (faster than what?), the nature of the effect (faster to do what?) and the population in whom this effect may be expected (faster in whom?). Some details of methodological approaches are reviewed, and suggestions for study designs are made.

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