scholarly journals Δ3,2-Hydroxybakuchiol Attenuates Depression in Multiple Rodent Models Possibly by Inhibition of Monoamine Transporters in Brain

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Gang Zhao ◽  
Li-he Guo ◽  
Wei Huang ◽  
Jia-liang Hu
Keyword(s):  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Rat Striatum ◽  
Mild Stress ◽  
Monoamine Transporters ◽  
Rodent Models ◽  
Norepinephrine Concentration ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Pheochromocytoma Pc12

Δ3,2-Hydroxybakuchiol is isolated fromPsoralea corylifolia (L.), which has therapeutic applications in traditional Chinese medicine. Our previous studies have showed that Δ3,2-hydroxybakuchiol inhibited the decreased activity of reserpinized mice, suggestive of its antidepressive potential. In this study, we explored the antidepressant profile of Δ3,2-hydroxybakuchiol in various rodent models and its possible monoamine-modulating mechanism. Δ3,2-Hydroxybakuchiol significantly reduced immobility time of mice in forced swim test and tail suspension test. Δ3,2-Hydroxybakuchiol also significantly increased sucrose consumption in chronic unpredictable mild stress (CUMS) rat model. Furthermore, isotope uptake study showed that Δ3,2-hydroxybakuchiol inhibited the activity of human dopamine transporter (DAT) and norepinephrine transporter (NET) in transporter-overexpressing pheochromocytoma (PC12) cells with IC50values similar to the potency of bupropion. Microdialysis showed that Δ3,2-hydroxybakuchiol increased dopamine and norepinephrine concentration in rat striatum. In summary, Δ3,2-hydroxybakuchiol exerts antidepressant effects on various types of depression models through a possible mechanism of monoamine transporter inhibition.

scholarly journals PERUBAHAN PERILAKU GROOMING DAN IMOBILITAS MENCIT BALB/C TERINDUKSI DEPRESI YANG DISUPLEMENTASI TEMPE SEBAGAI SUMBER PARAPROBIOTIK

2020 ◽  
Vol 14 (01) ◽  
pp. 1
Author(s):  
Vanessa Ardianty ◽  
Brian Saputra Manurung
Keyword(s):  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Tail Suspension Test ◽  
Depression Symptoms ◽  
Depression Symptom ◽  
Mild Stress ◽  
Immobility Time ◽  
Depression Level ◽  
The Common ◽  
Probiotic Food

Depression, a mental disorder marked by sadness, anhedonia and increased fatigability, is becoming more common in this industry 4.0 era. Nowadays, depression affects approximately 322 million people around the world (more than 14 million in Indonesia) and gives major contribution to the rise of global burden of disease. Although antidepressant is considered the common treatment for depression, recent studies show a possibility to treat depression by altering gut microbiome of the patient, by giving them probiotic food. Tempeh is a globally well-known Indonesian paraprobiotic food which already proven to modulate gut microbiota. This research aimed to find out the effect of tempeh to depression symptom as expressed in Balb/c mice behaviors. The methods used was to feed tempeh or tempeh starter to mice which were depressed-induced by Unpredictable Chronic Mild Stress (UCMS) procedure. Parameter measured were depression level of the Balb/c mice based on immobility times and grooming durations acquired from tail suspension test, forced swim test, sucrose splash test and coat state score. The result showed that tempeh supplementation did not affect coat states and grooming durations but tend to improve immobility times of the Balb/c mice. Meanwhile, tempeh starter supplementation tends to improve the immobility time and kept coat state clean/tidy, but lowered grooming duration. In conclusion, supplementation of paraprobiotic tempeh, especially in starter form, tend to improve depression symptoms. Keywords: depression, mice, paraprobiotic, tempeh

Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery

2015 ◽  
Vol 26 (1) ◽  
Author(s):  
Yeshwant Kurhe ◽  
Radhakrishnan Mahesh ◽  
Deepali Gupta ◽  
Devadoss Thangaraj
Keyword(s):  
Lipid Peroxidation ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Brain Homogenate ◽  
Therapeutic Interventions ◽  
Mild Stress ◽  
Behavioral Alterations ◽  
Biochemical Alterations ◽  
Immobility Time

AbstractThe inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HTAnimals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice were administered with (4a) (2 and 4 mg/kg p.o.), escitalopram (10 mg/kg p.o.), or vehicle (10 mL/kg p.o.) until day 28 along with the CUMS. Thereafter, behavioral battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), and elevated plus maze (EPM) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were estimated in the mice brain homogenate.(4a) Dose dependently attenuated the behavioral alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the open arm number of entries and time in EPM. Furthermore, biochemical alterations were reversed by (4a) as examined by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD.(4a) exhibits antidepressant potential by reversing the CUMS induced behavioral and biochemical changes in mice.

scholarly journals FGF21 restores hippocampual mitochondrial dysfunction via enhancing Nrf2/HO-1 and AMPK/SirT1/PGC-1α signaling pathways to alleviate chronic unpredictable mild stress induced depressive like behaviors in mice

2021 ◽  
Author(s):  
Yun-Tao Zhao ◽  
Ling Shen ◽  
Yong-Ping Zhang ◽  
Lulu Zhang ◽  
Leigang Jin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Expression Level ◽  
Fibroblast Growth Factor 21 ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Immobility Time

Abstract Mitochondrial dysfunction plays a key role in the pathogenesis of depression. Ample research proves mitochondria are a promising target for depression. Fibroblast growth factor 21 (FGF21) exerts roles in neuroprotection and could enhance mitochondria function. Here, the anti-depressive effect of FGF21 was evaluated on a chronic unpredictable mild stress (CUMS)- induced model of depression. The depressive-like behaviors were assessed using sucrose preference test (SPT), forced swim test (FST) and tail suspension test (TST). The results showed that treatment of FGF21 significantly attenuated the decrease in SPT, and dramatically reduced the immobility time in the TST and FST. These effects were associated with enhanced hippocampal mitochondrial function, reflected by FGF21-induced increases in mitochondrial ATP concentration, mitochondrial membrane potential (MMP), and decrease of reactive oxygen species (ROS) levels. At the same time, FGF21 ameliorated oxidative stress in CUMS-exposed mice by enhancing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase activities, and reducing malondialdehyde (MDA) level in the hippocampus. Mechanistically, we found that CUMS treatment decreased expression level of mitochondrial fusion protein 1 (MFN1), and increased expression level of mitochondrial dynamin-related protein 1 (DRP1). FGF21 administration increased expression of MFN1, and reduced expression of DRP1. Meanwhile, FGF21 treatment promoted the expression levels of Nrf2, HO-1, phosphorylated AMPK, SirT1, PGC-1a in the hippocampus. This study revealed that FGF21 alleviates CUMS induced depressive like behaviors by restoring mitochondria function via enhancing Nrf2/HO-1 and AMPK/SirT1/PGC-1α signaling pathways. It suggested that FGF21 would be a potential therapeutic agent in the management of depression.

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system

2018 ◽  
Vol 32 (4) ◽  
pp. 469-481 ◽  
Author(s):  
Yu-Fei Ni ◽  
Hao Wang ◽  
Qiu-Yan Gu ◽  
Fei-Ying Wang ◽  
Ying-Jie Wang ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Brain Derived Neurotrophic Factor ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antidepressant Effects ◽  
Bdnf Signaling

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

scholarly journals Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol

2021 ◽  
Vol 14 (12) ◽  
pp. 1269
Author(s):  
Gabriela P. Silote ◽  
Michelle C. Gatto ◽  
Amanda Eskelund ◽  
Francisco S. Guimarães ◽  
Gregers Wegener ◽  
...  
Keyword(s):  
Selective Breeding ◽  
Cannabis Sativa ◽  
Tail Suspension Test ◽  
Rodent Models ◽  
Tail Suspension ◽  
Resistant Lines ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Administration Time ◽  
Different Strains

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behavior. Moreover, only a few studies investigated the effect of CBD in female rodents. Therefore, we aimed to (i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects and (ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect 1 h post injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at 1 h and decreasing it at 2 h. In conclusion, strain, sex, and administration time affect CBD’s behavioral response to rodents exposed to tests predictive of antidepressant effects.

scholarly journals Systematic review of the antidepressant activity and associated antioxidant and anti-inflammatory effects of flavonoids in rodents

2021 ◽  
Vol 10 (12) ◽  
pp. e410101220673
Author(s):  
Lysrayane Kerullen David Barroso ◽  
Mateus Aragão Esmeraldo ◽  
Isaac Carioca De Oliveira ◽  
Miguel Costa Rodrigues Junior ◽  
Nickolas Souza Silva
Keyword(s):  
Systematic Review ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Specific Model ◽  
Mild Stress ◽  
Rodent Models ◽  
Scutellaria Baicalensis Georgi ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Introduction: Flavonoids have received an increasing attention from the scientific community in the last decade due to its antioxidant and anti-inflammatory effects, showing benefits in various conditions, including major depression in animal models. The aim of this study was to review the evidence produced in the last 10 years regarding the antidepressant, antioxidant and anti-inflammatory effect of flavonoids in rodent models of depression. Material and methods: It was performed a systematic review to gather articles published between 2009 and 2019 that evaluate those effects of flavonoids in rodent models of depression. Results: 43 studies were included in the review. The most frequently studied flavonoids were hesperidin (14%) and baicalin (9%). The major natural source of flavonoids were citrus fruits (19%) and Scutellaria baicalensis Georgi (9%).  Mice were used in the majority of the studies (86%). The majority of the studies did not use a specific model of depression (40%), and the most frequently used one was Chronic Unpredictable Mild Stress (21%). The most frequently used behavioral tests were forced swim test (81%), tail suspension test (56%) and open field test (51%). Discussion: Considering total tests, 93% of them presented an antidepressant activity, and all the studies that evaluated oxidative stress (37%) and inflammation (39%) found a significant antioxidant and anti-inflammatory result, respectively. Conclusions: Those findings demonstrate that the antidepressant, antioxidant and anti-inflammatory effects of flavonoids that were already evidenced in the study of other pathological conditions are also present in rodent depression models.

scholarly journals Strain, Sex, and Time Dependent Antidepressant-like Effects of Cannabidiol

2021 ◽  
Author(s):  
Gabriela Pandini Silote ◽  
Michelle C. Gatto ◽  
Amanda Eskelund ◽  
Francisco S. Guimarães ◽  
Gregers Wegener ◽  
...  
Keyword(s):  
Selective Breeding ◽  
Cannabis Sativa ◽  
Tail Suspension Test ◽  
Rodent Models ◽  
Resistant Lines ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Administration Time ◽  
Different Strains ◽  
Different Doses

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

2020 ◽  
Vol 16 (9) ◽  
pp. 1319-1327
Author(s):  
Ferdous Khan ◽  
Syed A. Kuddus ◽  
Md. H. Shohag ◽  
Hasan M. Reza ◽  
Murad Hossain
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reduced Glutathione ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Glutathione Depletion ◽  
Swim Test ◽  
Stress Markers ◽  
Immobility Time ◽  
Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

The Effect of Fluoxetine and Ibuprofen on BCG-Induced Alteration in Pain Sensitivity in Mice

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Heba H El-Morsy ◽  
Wesam El-Bakly ◽  
Amany H Hasanin ◽  
May Hamza ◽  
M Abdel-Bary
Keyword(s):  
Drinking Water ◽  
Mechanical Allodynia ◽  
Formalin Test ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Control Group ◽  
Base Line ◽  
Immobility Time ◽  
Long Time ◽  
Incisional Pain

Abstract Clinical observations recognized the co-existence and interactions of pain and depression a long time, ago. The aim of this work was to study the effect of ibuprofen and fluoxetine on BCGinduced depressive-like behaviour, on formalin-induced pain, as well as on mechanical allodynia after planter incision in mice. BCG induced a depressive behaviour that was seen in the forced swim test (FST) and the tail suspension test (TST). It also induced a decrease in pain-related behaviour in the formalin test, and an increase in the baseline in mechanical allodynia test compared to the control group. Fluoxetine (80 mg/L of drinking water) showed a significant decrease in the immobility time in the FST and TST and enhanced pain related behaviour in formalin test in the BCG-inoculated group. However, it did not affect the increase in the pain threshold in the planter incision allodynia model. Adding ibuprofen to drinking water (0.2 g/L of drinking water), reversed the depressive like behaviour induced by BCG and enhanced pain-related behaviour in formalin test, in both the total pain-related behaviour and phase 2. It also prevented the increase in the base line induced by BCG. On the other hand, the incisional pain model was not affected by BCG inoculation except at the 2-hour time point, where it showed hypoalgesia, as well.

scholarly journals Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

2018 ◽  
Vol 33 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Jaclyn N Highland ◽  
Patrick J Morris ◽  
Panos Zanos ◽  
Jacqueline Lovett ◽  
Soumita Ghosh ◽  
...  
Keyword(s):  
Oral Administration ◽  
Learned Helplessness ◽  
Oral Bioavailability ◽  
Forced Swim Test ◽  
Abuse Potential ◽  
Absolute Bioavailability ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

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