Astressin, an antagonist of CRF receptors, reduces anxiety and fobial states in rats reared in social isolation conditions

2016 ◽  
Vol 14 (4) ◽  
pp. 24-31 ◽  
Author(s):  
Andrei A Lebedev ◽  
Anna G Pshenichnaya ◽  
Eugenii R Bychkov ◽  
Natalia D Yakushina ◽  
Petr D Shabanov
Keyword(s):  
Social Isolation ◽  
Intranasal Administration ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Emotional Behavior ◽  
Isolation Stress ◽  
Delayed Effects ◽  
Plus Maze ◽  
And Behavior ◽  
Anxiety And Fear

The influence of intranasal administration of astressin, a nonselective antagonist of CRF receptors, on delayed effects of chronic social isolation in the five first weeks after mother leaving on explorative and emotional behavior in rats was studied. Social exposures were applied from 21st to 93rd days of life. The rats reared in social isolation demonstrated higher level of motor activity compared with control in open field test. The assessment of both anxiety and fobial state and behavior in elevated plus maze revealed higher levels in anxiety and fear in isolated rats. Intranasal administration of astressin (1 µg/1µl, 20 µl, 10 µl in every nostrils) reduced significantly anxiety and fear levels in isolated rats. Therefore, both anxiolytic and antifobial effects of astressin, a nonselective antagonist of CRF receptors, were demonstrated in rats exposured to social isolation stress. The results support the idea taking into account the corticoliberin mechanisms in formation of social isolation syndrome and possibilities of using CRF antagonists to control the central stress mechanisms and dependence in ontogeny.

scholarly journals Effect of astressin, a corticoliberin antagonist, on aggression and anxiety-fobic states in male rats reared in social isolation

2017 ◽  
Vol 15 (3) ◽  
pp. 38-47
Author(s):  
Andrei A. Lebedev ◽  
Anna G. Pshenichnaya ◽  
Natalia D. Yakushina ◽  
Eugenii R. Bychkov ◽  
Petr D. Shabanov
Keyword(s):  
Motor Activity ◽  
Social Isolation ◽  
Intranasal Administration ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Male Rats ◽  
Plus Maze ◽  
The Social ◽  
Anxiety And Fear ◽  
Intraspecific Behavior

Aim. Intraspecific behavior, emotional and explorative activity were investigated after intranasal administration of astressin, a non-selective antagonist of CRF receptors, in the male rats reared in social isolation from 21 to 93 days. Results. In the “resident-intruder” test there was an increased level of aggression and communications in isolated rats compared to grouped animals. After intranasal administration of astressin (20 μg in 20 μl), rats grown in isolation demonstrated an increase in aggression and decreased in communicability compared to intact animals reared in isolation. In the “open field” test a level of motor activity was increased in rats grown in isolation compared to grouped animals. The anxiety-phobic state, as well as behavior in an elevated plus maze, revealed enhance of anxiety and fear in rats reared in isolation. After astressin administration to isolated animals the levels of anxiety and fear significantly decreased. Conclusion. The results of the work revealed that the antagonist of the CRF receptor astressin disinhibited aggression, removing anxious and phobic state in male rats reared in social isolation. The results prove the necessity of taking into account CRF mechanisms in the formation of the social isolation syndrome and the possibility of using CRF receptor antagonists to control the central mechanisms of stress and dependence in ontogenesis.

Pharmacological analysis of the effects of the neuropeptide Y antagonist BMS 193885 on the emotional, intraspecies behavior and reinforcing properties of ethanol in rats

2020 ◽  
Vol 18 (2) ◽  
pp. 131-138
Author(s):  
Aleksander R. Moskalyev ◽  
Maxim E. Abrosimov ◽  
Eduard A. Vetlugin ◽  
Anna G. Pshenichnaya ◽  
Ilya Yu. Tissen ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Open Field ◽  
Field Test ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Emotional Behavior ◽  
Intraspecific Interaction ◽  
Plus Maze ◽  
Resident Intruder

Purpose. Our previously data on orexigenic peptides (orexin, ghrelin) showed antagonists of peptides receptors as correctors of the emotional-motivational and cognitive spheres. Currently, a close relationship between ghrelin and orexin with neuropetide Y has been shown in feeding and emotional behavior. The aim of this work was to analyze the effect of the NPY antagonist Y1R BMS 193885 on emotional and intraspecies behavior, as well as on the reinforcing properties of ethanol in rats. Methods. We used the open field test, elevated plus-maze, Porsolts forced swimming test, resident intruder test, conditional place preference (CPP). BMS 193885 1 mg/ml, 20 l intranasally did not cause an anxiogenic effect in the elevated plus-maze. Results. In the Porsolts test, there was also no increase in the level of depression. Moreover, there was a significant decrease in the number and time of dives, as an indirect indicator of a decrease in the level of depression. At the same time, in the resident intruder test were decreased protective behavior, as an indicator of a decrease in the stress of intraspecific interaction in the absence of aggression. Moreover, local movements were increased in the open field test as an indicator of the animals activity impaired by fear. BMS 193885 had no effect on the expression of the CPP of ethanol. Conclusion. Thus, it was previously shown that the BMS 193885 is a powerful, selective, brain-penetrating Y1 receptor antagonist, it reduces food intake and body weight in animal models of obesity both after acute and chronic administration. Our data indicate that the decrease in food intake is not associated with the level of anxiety, depression, or with a change in intraspecific interaction. It has been previously shown that NPY reduces alcohol consumption. Our data indicate that the Y1R antagonist of the neuropeptide Y BMS 193885 does not cause a change in the CPP of alcohol.

scholarly journals Participation ofGABAAChloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Juan Francisco Rodríguez-Landa ◽  
Rosa Isela García-Ríos ◽  
Jonathan Cueto-Escobedo ◽  
Blandina Bernal-Morales ◽  
Carlos M. Contreras
Keyword(s):  
Open Field ◽  
Field Test ◽  
Chloride Channels ◽  
Wistar Rats ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Acid Mixture ◽  
Plus Maze ◽  
Gaba Binding ◽  
Defensive Burying

Human amniotic fluid and a mixture of eight fatty acids (FAT-M) identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg%) produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement ofγ-aminobutyric acid-A (GABAA) receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, threeGABAAreceptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg),GABAAbenzodiazepine antagonist flumazenil (5 mg/kg), and noncompetitiveGABAAchloride channel antagonist picrotoxin (1 mg/kg). The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. TheGABAAantagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects throughGABAAreceptor chloride channels.

scholarly journals The novel dipeptide ligand of TASP

2019 ◽  
Vol 484 (2) ◽  
pp. 228-232
Author(s):  
O. A. Deeva ◽  
A. S. Pantileev ◽  
I. V. Rybina ◽  
M. A. Yarkova ◽  
T. A. Gudasheva ◽  
...  
Keyword(s):  
Elevated Plus Maze ◽  
Open Field Test ◽  
Anxiolytic Activity ◽  
The Novel ◽  
Minimum Effective Dose ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Order Of Magnitude ◽  
Preliminary Administration

Using the previously obtained first dipeptide ligand TSPO the N‑carbobenzoxy-L‑tryptophanyl-L‑isoleucine amide (GD‑23) as a basis, the new dipeptide was synthesized — the N‑phenylpropionyl–L‑tryptophanyl-L‑leucine amide (GD‑102). GD‑102 expressed anxiolytic activity in the open field test in BALB/c mice and in the elevated plus maze test in ICR mice. The minimum effective dose of GD‑102 was an order of magnitude lower than that of GD‑23. Preliminary administration of the TSPO selective antagonist, compound PK11195, completely blocked the anxiolytic activity of GD‑102, that indicated the participation of TSPO in the realization of the anxiolytic action GD‑102. The results were confirmed by molecular docking data.

scholarly journals PPAR-α Hypermethylation in the Hippocampus of Mice Exposed to Social Isolation Stress Is Associated with Enhanced Neuroinflammation and Aggressive Behavior

2021 ◽  
Vol 22 (19) ◽  
pp. 10678
Author(s):  
Francesco Matrisciano ◽  
Graziano Pinna
Keyword(s):  
Social Isolation ◽  
Histone Deacetylases ◽  
Epigenetic Modification ◽  
Emotional Behavior ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Isolation Stress ◽  
Social Isolation Stress ◽  
Socially Isolated

Social behavioral changes, including social isolation or loneliness, increase the risk for stress-related disorders, such as major depressive disorder, posttraumatic stress disorder (PTSD), and suicide, which share a strong neuroinflammatory etiopathogenetic component. The peroxisome-proliferator activated receptor (PPAR)-α, a newly discovered target involved in emotional behavior regulation, is a ligand-activated nuclear receptor and a transcription factor that, following stimulation by endogenous or synthetic ligands, may induce neuroprotective effects by modulating neuroinflammation, and improve anxiety and depression-like behaviors by enhancing neurosteroid biosynthesis. How stress affects epigenetic mechanisms with downstream effects on inflammation and emotional behavior remains poorly understood. We studied the effects of 4-week social isolation, using a mouse model of PTSD/suicide-like behavior, on hippocampal PPAR-α epigenetic modification. Decreased PPAR-α expression in the hippocampus of socially isolated mice was associated with increased levels of methylated cytosines of PPAR-α gene CpG-rich fragments and deficient neurosteroid biosynthesis. This effect was associated with increased histone deacetylases (HDAC)1, methyl-cytosine binding protein (MeCP)2 and decreased ten-eleven translocator (TET)2 expression, which favor hypermethylation. These alterations were associated with increased TLR-4 and pro-inflammatory markers (e.g., TNF-α,), mediated by NF-κB signaling in the hippocampus of aggressive mice. This study contributes the first evidence of stress-induced brain PPAR-α epigenetic regulation. Social isolation stress may constitute a risk factor for inflammatory-based psychiatric disorders associated with neurosteroid deficits, and targeting epigenetic marks linked to PPAR-α downregulation may offer a valid therapeutic approach.

scholarly journals Sensitivity to diazepam after a single session of forced swim stress in weaning Wistar rats

2018 ◽  
Vol 68 (3) ◽  
pp. 381-388 ◽  
Author(s):  
Blandina Bernal-Morales ◽  
Gabriel Guillén-Ruiz ◽  
Jonathan Cueto-Escobedo ◽  
Juan Francisco Rodríguez-Landa ◽  
Carlos M. Contreras
Keyword(s):  
Wistar Rats ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Clinical Applications ◽  
Minimum Effective Dose ◽  
Single Session ◽  
Adult Rats ◽  
Stressed Group ◽  
Plus Maze ◽  
Forced Swim Stress

Abstract The present study investigated the sensitivity to stress and diazepam in weaning (21-day old) Wistar rats. A single 15-min session of forced swimming was used to induce anxiety-like behavior. The group that was forced to swim exhibited an increase in anxiety-like behavior in the elevated plus maze (EPM) and open field test (OFT) compared to the non-stressed group. Diazepam (1 h before the tests) reduced anxiety-like behavior in rats forced to swim compared to the vehicle stressed group. The dose-response curve for diazepam indicated that the 0.5 mg kg−1 dose (1 h before the EPM and OFT) was the minimum effective dose in reducing anxiety-like behavior without altering locomotor activity in weaning rats. These results indicate that weaning rats can develop anxiety-like behavior after a brief, single session of stress, and that rats at this age are seemingly more sensitive to diazepam than adult rats, which may be taken into account for clinical applications.

scholarly journals Effect on Emotional Behavior and Stress by Inhalation of the Essential oil from Chamaecyparis obtusa

2013 ◽  
Vol 8 (4) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Hikaru Kasuya ◽  
Erika Hata ◽  
Tadaaki Satou ◽  
Masaki Yoshikawa ◽  
Shinichiro Hayashi ◽  
...  
Keyword(s):  
Essential Oil ◽  
Elevated Plus Maze ◽  
Growth Factor Receptor ◽  
Glass Container ◽  
Chamaecyparis Obtusa ◽  
Emotional Behavior ◽  
Antibacterial And Antifungal Activity ◽  
Plus Maze ◽  
Antibacterial And Antifungal ◽  
The Brain

Various effects have been reported in the literature for the essential oil from Chamaecyparis obtusa (EOCO), such as antibacterial and antifungal activity. In this study, we examined the effect of EOCO on emotional behavior and stress-induced biomarkers. Male ICR mice, aged 5 weeks at the start of each experiment, were individually housed in cages for 1 week. After placing each mouse in a glass container and exposing it to EOCO for 90 min, we then investigated the influence on emotional behavior using the elevated-plus maze (EPM) test, which is one of the evaluation methods for anxiolytic-like behavior. Significant anxiolytic-like effects were observed for the 7.0 mg/L air EOCO ( P<0.05). After the EPM test, mice were dissected and changes in the stress-induced biomarkers within the brain were investigated by examining the amounts of fast nerve growth factor receptor (NGFR) and activity regulated cytoskeletal-associated protein (Arc) gene expression, and brain-derived neurotrophic factor (BDNF) and galactokinase 1 (GLK1) protein expression. Significant increases were observed in the amount of NGFR after inhalation of 7.0 mg/L air EOCO ( P<0.05). These results indicate that EOCO has both anxiolytic-like and stress mitigation effects.

scholarly journals Antidepressant-Like Effect ofIlex paraguariensisin Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Elizete De Moraes Reis ◽  
Francisco Waldomiro Schreiner Neto ◽  
Vitória Berg Cattani ◽  
Luis Ricardo Peroza ◽  
Alcindo Busanello ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Monoamine Oxidase ◽  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Forced Swimming ◽  
Monoamine Oxidase Activity ◽  
Plus Maze ◽  
Thiol Content ◽  
Swimming Test

In this study, we investigated the possible antidepressant-like effect ofI. paraguariensisin rats. Rats were treated for four weeks with an aqueous extract ofI. paraguariensisin drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours ofI. paraguariensisintake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile ofI. paraguariensisextract.I. paraguariensisreduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect ofI. paraguariensiswas observed in rats through the elevated plus-maze test. The antidepressant-like effect ofI. paraguariensiswas not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract ofI. paraguariensisdecreases the time of immobility in rats suggesting an antidepressant-like effect.

scholarly journals Modulating Effects of Cholecalciferol Treatment on Estrogen Deficiency-Induced Anxiety-Like Behavior of Adult Female Rats

Folia Medica ◽  
2017 ◽  
Vol 59 (2) ◽  
pp. 139-158 ◽  
Author(s):  
Julia Fedotova ◽  
Daria Zarembo ◽  
Jozef Dragasek ◽  
Martin Caprnda ◽  
Peter Kruzliak ◽  
...  
Keyword(s):  
Elevated Plus Maze ◽  
Open Field Test ◽  
Estrogen Deficiency ◽  
Female Rats ◽  
Ovx Rats ◽  
Plus Maze ◽  
17Β Estradiol ◽  
Experimental Rat Model ◽  
High Doses ◽  
Estradiol 17Β

AbstractBackground:Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance.Materials and methods:The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were assessed in the open-field test (OFT).Results:Cholecalciferol in high doses alone or in combination with 17β-E2-induced anxiolytic-like effects in OVX and OVX rats treated with 17β-E2as evidenced in the EPM and LDT tests, and increased grooming activity in the OFT test. We found that DA and 5-HT levels increased while 5-HT turnover in the hippocampus decreased in these groups of OVX rats.Conclusion:Our results indicate that cholecalciferol in high doses has a marked anxiolytic-like effect due to an increase in the monoamines levels in the experimental rat model of estrogen deficiency.

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