Cortical 5-hydroxytryptamine 1A receptor biased agonist, NLX-101, displays rapid-acting antidepressant-like properties in the rat chronic mild stress model

2019 ◽  
Vol 33 (11) ◽  
pp. 1456-1466 ◽  
Author(s):  
Ronan Depoortère ◽  
Mariusz Papp ◽  
Piotr Gruca ◽  
Magdalena Lason-Tyburkiewicz ◽  
Monika Niemczyk ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Duration Of Action ◽  
Plus Maze ◽  
Antidepressant Effects ◽  
Extended Duration ◽  
Cessation Of Treatment ◽  
Biased Agonist

Background:NLX-101 (also known as F15599) is a highly selective and efficacious ‘biased’ agonist at cortical 5-hydroxytryptamine 1A (5-HT1A) heteroreceptors. In rodents, it possesses marked antidepressant-like activity, potently and completely abolishing immobility in the forced swim test (FST) with extended duration of action.Methods:We investigated the antidepressant-like activity of NLX-101 using the rat chronic mild stress (CMS) model of depression, considered to have a higher translational potential than the FST, as it possesses construct, face and predictive validity. The effects of CMS and repeated NLX-101 treatment were tested using sucrose consumption (a measure of anhedonia), novel object recognition (NOR; a measure of working memory) and elevated plus maze (EPM; a measure of anxiety) tests.Results:NLX-101 reversed the CMS-induced decrease of sucrose intake on day 1 of testing, with full reversal observed at the dose of 0.16 mg/kg and a less pronounced but still significant effect at 0.04 mg/kg, both given twice a day intraperitoneally. The effects of NLX-101 were maintained over the 2 week treatment period and persisted for four weeks following cessation of treatment. In the NOR test, both doses of NLX-101 rescued the deficit in discrimination index caused by CMS, without any effect on locomotor activity. However, NLX-101 had no effect on the reduction of open-arms entries produced by CMS in the EPM model. In control, non-stressed rats, NLX-101 produced non-significant effects in all three models.Conclusions:NLX-101 displayed efficacious activity in the CMS test, with more rapid (1 day) antidepressant-like effects than pharmacological compounds tested previously under the same experimental conditions. These observations suggest that biased agonist targeting of cortical 5-HT1Areceptors constitutes a promising strategy to achieve rapid-acting and sustained antidepressant effects.

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 Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Male Rats ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Glucocorticoid Responsive Element ◽  
Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

scholarly journals Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Anastasiya Kasian ◽  
Timur Kolomin ◽  
Lyudmila Andreeva ◽  
Elena Bondarenko ◽  
Nikolay Myasoedov ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Anxiolytic Effect ◽  
Chronic Mild Stress ◽  
Stress Conditions ◽  
Mild Stress ◽  
Unpredictable Chronic Mild Stress ◽  
Elevated Plus Maze Test ◽  
Plus Maze ◽  
The Individual ◽  
Benzodiazepine Drugs

It was shown that the anxiolytic effect of Selank is comparable to that of classical benzodiazepine drugs and that the basis of their mechanism of action may be similar. These data suggest that the presence of Selank may change the action of classical benzodiazepine drugs. To test this hypothesis, we evaluated the anxiolytic activity of Selank and diazepam in rats both under conditions of unpredictable chronic mild stress and in its absence, after the individual and combined administration of these compounds using the elevated plus maze test. We found that, even in the absence of chronic stress, the administration of a course of test substances changed anxiety indicators toward their deterioration, but the changes after the administration of a course of Selank were less pronounced. In conditions of chronic stress, anxiety indicator values after the simultaneous use of diazepam and Selank did not differ from the respective values observed before chronic stress exposure. The data obtained indicate that the individual administration of Selank was the most effective in reducing elevated levels of anxiety, induced by the administration of a course of test substances, whereas the combination of diazepam with Selank was the most effective in reducing anxiety in unpredictable chronic mild stress conditions.

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

Evaluation of the antidepressant-like effect of chronic administration of Nigella fixed oil versus fluoxetine in rats

2021 ◽  
Vol 20 ◽  
Author(s):  
Youness Kadil ◽  
Imane Tabyaoui ◽  
Latifa Badre ◽  
Nadia Tahiri Jouti ◽  
Houda Filali
Keyword(s):  
Nigella Sativa ◽  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Chronic Administration ◽  
Histopathological Analysis ◽  
Mild Stress ◽  
Behavioral Test ◽  
Histological Changes ◽  
Swim Test ◽  
Therapeutic Properties

Background: Depression is a group of syndromes characterized by notable and persistent mood disorders, and is one of the most prevalent psychiatric disorders, while the existing treatments have an altered risk-benefit balance. The therapeutic properties of Nigella have been confirmed, suggesting the reliance on phytotherapy. The objective of the present paper is to investigate the antidepressive-like effect of Nigella sativa on rats exposed to the Unpredictable Chronic Mild Stress procedure. Methods: Wistar rats were used to investigate the antidepressive-like effect. The stress procedure used in this study combined many stressful conditions. After 6 weeks of treatment, behavioral test (forced swim test) was conducted, and histological changes of the hippocampus were examined. Results: Treatment by nigella and fluoxetine significantly reduced the struggling time. Conclusion: Histopathological analysis showed that control treatments result in more loosely arranged cells, significant apoptotic neurons characterized by an irregular appearance, and pyknotic hyperchromatic. A reduction of the thickness of the pyramid layer was also observed in the groups treated with nigella and fluoxetine, suggesting that nigella could be used as a treatment or an adjuvant preventing depressive-like disorders.

Evaluation of the antianxiety and antidepressant activities of mosapride in Wistar albino rats

2019 ◽  
Vol 30 (4) ◽  
Author(s):  
Vybhava Krishna ◽  
KL Bairy ◽  
Navin Patil ◽  
Sweenly V. Sunny
Keyword(s):  
Forced Swim Test ◽  
Sucrose Preference ◽  
Albino Rats ◽  
High Dose ◽  
Low Doses ◽  
Chronic Unpredictable Stress ◽  
Investigational Drugs ◽  
Plus Maze ◽  
Antidepressant Effects ◽  
Wistar Albino Rats

Abstract Background The 5HT4 receptor agonists are antidepressants with a unique mode of action. Many studies have been done on investigational drugs, and mosapride has been shown to have a 5HT3 antagonistic property. In this study, we assessed the potential anxiolytic and antidepressant effects of mosapride on Wistar albino rats. Methods The rats were randomly assigned to two models containing 4 groups of 6 animals each. In the anxiety model, four groups included 0.5 mL of 0.5% carboxymethyl cellulose (CMC), mosapride 1.5 mg/kg, mosapride 3 mg/kg and diazepam 2 mg/kg. They were dosed for 5 days. On the 3rd day, the elevated plus maze (EPM) was conducted, and on the 5th day, the open field (OF) tests were conducted. In the depression model, four groups included 0.5 mL of 0.5% CMC, mosapride 1.5 mg/kg, mosapride 3 mg/kg and imipramine 30 mg/kg. After 3 days of dosing, the forced swim test (FST) was conducted, followed by a washout period of 1 month. Then, the rats were subjected to chronic unpredictable stress with sucrose preference. Results Compared with the control, the mosapride-treated animals showed significant anxiolytic behavior at both high and low doses in the EPM and OF tests. In the FST, both high and low doses of mosapride reduced immobility. The climbing behavior was prominent at a high dose of mosapride, whereas swimming was prominent at a low dose. In the chronic stress model, both doses of mosapride preserved sucrose preference comparable to imipramine. Conclusion These findings suggest that mosapride has anxiolytic and antidepressant activities at clinically used doses.

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