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.

Oral supplementation with geranium oil or anise oil ameliorates depressed rat-related symptoms through oils antioxidant effects

2019 ◽  
Vol 17 (2) ◽  
Author(s):  
Karima A. El-Shamy ◽  
Khaled M. M. Koriem ◽  
Nevein N. Fadl ◽  
Marwa H. A. El-Azma ◽  
Mahmoud S. S. Arbid ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Oral Intake ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Psychiatric Disease ◽  
Albino Rats ◽  
Mild Stress ◽  
Immobility Time ◽  
Antioxidant Effects

AbstractBackgroundDepression is a psychiatric disease condition and the chronic mild stress (CMS) model is a well-known and valuable animal model of depression. Geranium oil and anise oil were chosen for such a study. The aim of this research was to establish the geranium oil and anise oil effect to ameliorate CMS-related symptoms.MethodsThis research included 80 male albino rats each group of 10 rats and the animals were divided into two major groups: normal and CMS. The normal group was subdivided into four (control, geranium oil, anise oil and venlafaxine drug) subgroups treated orally with saline, geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. The CMS group was subdivided into four (CMS without any treatment, CMS + geranium oil, CMS + anise oil and CMS + venlafaxine drug) subgroups treated orally with geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks.ResultsThe sucrose consumption in sucrose preference test, the distance traveled test and center square entries test were decreased, while center square duration test, immobility time in tail suspension test and floating time in forced swimming test were increased in CMS. The superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase levels decreased but malondialdehyde and nitric oxide levels increased in brain cerebral cortex and hippocampus areas in CMS. The oral intake of geranium oil and anise oil pushes all these parameters to approach the control levels. These results were supported by histopathological investigations of both brain cerebral cortex and hippocampus tissues.ConclusionsGeranium oil and anise oil ameliorate CMS-related symptoms and this effect were related to the antioxidant effects of oils.

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

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 The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Haixia Wang ◽  
Hong Huang ◽  
Jingwei Lv ◽  
Guirong Zeng ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Forced Swim Test ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Oxidative Markers ◽  
Immobility Time ◽  
Polygala Tenuifolia ◽  
Sucrose Preference Test

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

scholarly journals Putative Role of Monoaminergic Systems in Antidepressant and Anxiolytic Effects of Naringin in Mice: An Interaction Study with Receptor Antagonists

2021 ◽  
pp. 661-676
Author(s):  
G. E. Anyanwu ◽  
V. O. Atuadu ◽  
B. Ben-Azu ◽  
E. A. Esom ◽  
J. N. Nto ◽  
...  
Keyword(s):  
Anxiolytic Effect ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Receptor Interaction ◽  
Control Group ◽  
Mild Stress ◽  
Receptor Antagonists ◽  
Neurotransmitter Receptor ◽  
Immobility Time

Aim: Stress-related disorders like depression and anxiety represent one of the greatest therapeutic challenges globally. Although previous studies have revealed the antidepressant-like potentials of naringin, the neurotransmitter receptor interaction mechanisms of action have not been studied, hence, this study was carried out to evaluate the role of neurotransmitter-receptor antagonists in the antidepressant-like effects of naringin in mice. Method: Male Swiss mice were subjected to chronic unpredictable mild stress (CUMS) apart from mice in the control group. The mice were then pretreated with different neurotransmitter antagonists; metergoline (4 mg /kg i.p.), a 5-HT1 - and 5-HT2 -receptor antagonist; propranolol; (0.2 mg/kg i.p.), β1,2-noradrenoceptor antagonist or haloperidol (0.2 mg/kg i.p.), D 2 -dopaminergic receptor antagonists prior to the administration of naringin or vehicle (10 mL/kg). The antidepressant-like and anxiolytic effects of naringin were evaluated 30 min later using the tail suspension test (TST), open-field test (OFT), sucrose preference test (SPT) and elevated plus maze (EPM) tests paradigms. Results: Administration of naringin following CUMS significantly decrease immobility time and locomotion activity in TST and OFT respectively, relative to control while increasing preference to sucrose in SPT, open arm entries as well as time spent in open arm in EPM, relative to control suggesting antidepressant-like property. Pretreatment with metergoline, propranolol, and haloperidol following CUMS increased immobility time in TST, locomotor activity in OFT and IOAA in the EPM. Reduced preference for sucrose in SPT, open arm entry and duration in EPM relative to control (p < 0.05), however, these effects were attenuated by naringin. Conclusion: These findings suggest that the antidepressant-like activity exhibited by naringin might be mediated via interactions with 5-HTergic, noradrenergic, and dopaminergic receptors, while the anxiolytic effect might involve interaction with both 5-HTergic and noradrenergic receptors.

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.

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 Lycopene Treatment Transposed Antidepressant-Like Action in Rats Provoked to Chronic Mild Stress

2019 ◽  
Vol 12 (2) ◽  
pp. 981-988
Author(s):  
Venkata Naveen Kumar P. ◽  
Elango P. ◽  
Asmathulla S. ◽  
Kavimani S
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Behavioral Changes ◽  
Mild Stress ◽  
Plus Maze ◽  
Immobility Time ◽  
Sucrose Preference Test

The present study aimed at evaluating the effects of lycopene on CMS-induced depressive-like behavioral changes in Wistar rats. In present study, rodents were selected randomly and grouped in to seven groups. Each group consists of six animals. All the groups are subjected to chronic mild stress in an unpredictable manner except the control group, which is free from stress. Behavioral changes induced during chronic mild stress were assessed by conducting the behavioral tests like forced swim test, sucrose preferences test, elevated plus maze test and open field tests in screening depressant and anxiety activity. The data analysis showed chronic mild stress produced depressive and anxiogenic behavior in the experimental rats. A significant increase in the immobility time and decrease in sucrose consumption in sucrose preference test are noted in CMS and vehicle groups. Similarly, in an elevated plus maze a significant decrease in the entries in the open arm and decrease in central square entries, and rearing behavior and increase in the duration of immobility were observed in open field test.Lycopene treatment for 6-weeks significantly decreased immobility time and increased in sucrose consumption observed in the forced swim test and sucrose preference test respectively. Lycopene significantly increased number of entries in the open arm of elevated plus maze and decreased grooming and freezing behavior in open field method. lycopene supplemented dose of 5mg/kg showed an insignificant results in all the behavioral models (p>0.05).The data were expressed as Mean±SD.Data were analyzed and differences between the means were determined by one-way analysis of variance (ANOVA) Using graph pad prism version 5.03 statistical software. In all the tests, differences were considered significant if p<0.05 to be a statistical significant. lycopene possesses antidepressant and mild- anxiolytic activity which may be due to its antioxidant effect that might warrant further studies.

scholarly journals An experimental study to evaluate the role of aspirin and metformin in prevention of depression in rats

2020 ◽  
Vol 9 (4) ◽  
pp. 605
Author(s):  
Alisha Abbas ◽  
Narendra Kumar ◽  
Sarvesh Singh ◽  
Rahul Kumar ◽  
Akhlaque Ahmad ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Preference Test ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Neurotransmitter System ◽  
Treatment Focus ◽  
Immobility Time ◽  
Current Therapies ◽  
Sucrose Preference Test

Background: Depression was seen to be associated with an increased level of inflammatory biomarkers along with the disturbance in the monoamine neurotransmitter system. Current therapies are mostly focussed on the neurotransmitters imbalance but due to increasing cases of treatment failure there is a need to shift our treatment focus to other potential therapies. This study aimed to evaluate the preventive role of aspirin and metformin in stress induced model of depression in wistar rats.Methods: Fifty four wistar rats were randomly divided into nine groups as normal control, experimental control, aspirin (30 mg/kg, 60 mg/kg), metformin (50 mg/kg, 100 mg/kg), two combination groups and imipramine (15 mg/kg). Depression model was created by the induction of chronic unpredictable mild stress (CUMS) for consecutive 28 days. Behavioural assessment was done by evaluating immobility time in forced swim test (FST) and sucrose preference ratio (SPR) in sucrose preference test. The data were analysed by analysis of variance (ANOVA) test using SPSS software. P<0.05 was considered to be statistically significant.Results: The CUMS led to an increase in immobility time and decrease in SPR. Aspirin and Metformin alone and their combinations showed statistically significant response in preventing the immobility time to increase (p<0.001) and SPR to decrease (p<0.001). However the response of Aspirin was comparable with Imipramine but the response of Metformin was not as significant as of Imipramine (p>0.05).Conclusions: Aspirin and metformin might have a potential role in the prevention of depression.

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