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

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.

2016 ◽  
Vol 14 (4) ◽  
pp. 24-31 ◽  
Author(s):  
Andrei A Lebedev ◽  
Anna G Pshenichnaya ◽  
Eugenii R Bychkov ◽  
Natalia D Yakushina ◽  
Petr D Shabanov

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.


2021 ◽  
Vol 0 (0) ◽  
pp. 1-22
Author(s):  
Elnaz Azizi ◽  
◽  
Fatemeh Ayoobi ◽  
Ali Shamsizadeh ◽  
Amir Moghadam-Ahmadi ◽  
...  

Introduction: Lack of high-quality sleep causes serious side effects like anxiety and changes in plasma concentration of oxalate. The current study aimed to investigate the impact of local extremely low frequency magnetic fields (ELF-MFs) on inducing sleep (sleepiness) and anxiety in male rats. Methods: In this experimental study, 40 male rats were allocated in four groups (n=10). The ELF-MFs exposure (0, 10 and 18 Hz) was applied with intensity 200µT for three days (10 min/day). Sham-treated animal did not receive ELF-MF. Serum level of oxalic acid (OA) and sleepiness were measured both before first and after last exposure to ELF-MF or sham. Anxiety, sleepiness and OA were measured by using elevated plus maze, open-field test (OFT) and ELISA test, respectively. Results: Comparison of oxalate levels between before and after exposure to ELF-MF revealed that ELF-MF (10 Hz) decreased the serum level of oxalate (p<0.05). Comparison of the percent of open:closed arm entry (in elevated plus maze) between before and after exposure to ELF-MF revealed significant differences. Also, frequency, velocity and distance moved were decreased in the open-field test. Conclusion: Results of the present study demonstrated that ELF-MF with short time exposure may modulate the metabolism of OA and may modulate anxiety-like behavior or kind of induction of sleepiness in male rats.


2019 ◽  
Vol 3 ◽  
pp. 247054701989703
Author(s):  
Jorge A. Sierra-Fonseca ◽  
Lyonna F. Parise ◽  
Francisco J. Flores-Ramirez ◽  
Eden H. Robles ◽  
Israel Garcia-Carachure ◽  
...  

Background Anxiety disorders are the most common neuropathologies worldwide, but the precise neuronal mechanisms that underlie these disorders remain unknown. The hippocampus plays a role in mediating anxiety-related responses, which can be modeled in rodents using behavioral assays, such as the elevated plus maze. Yet, the molecular markers that underlie affect-related behavior on the elevated plus maze are not well understood. Methods We used herpes simplex virus vector delivery to overexpress extracellular signal-regulated kinase-2, a signaling molecule known to be involved in depression and anxiety, within the dorsal hippocampus of adult Sprague-Dawley male rats. Three days post virus delivery, we assessed anxiety-like responses on the elevated plus maze or general locomotor activity on the open field test. Results When compared to controls, rats overexpressing extracellular signal-regulated kinase-2 in the dorsal hippocampus displayed an anxiolytic-like phenotype, per increases in time spent in the open arms, and less time in the closed arms, of the elevated plus maze. Furthermore, no changes in locomotor activity as a function of virus infusion were observed on the open field test between the experimental groups. Conclusion This investigation demonstrates that virus-mediated increases of extracellular signal-regulated kinase-2 signaling, within the hippocampus, plays a critical role in decreasing anxiogenic responses on the rat elevated plus maze. As such, our data provide construct validity, at least in part, to the molecular mechanisms that mediate anxiolytic-like behavior in rodent models for the study of anxiety.


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

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Changhong Gu ◽  
ZhengLin Zhao ◽  
Xiaodong Zhu ◽  
Tong Wu ◽  
Bong Hyo Lee ◽  
...  

Anxiety during nicotine withdrawal (NicW) is a key risk factor for smoking relapse. Semen Ziziphi Spinosae (SZS), which is a prototypical hypnotic-sedative herb in Oriental medicine, has been clinically used to treat insomnia and general anxiety disorders for thousands of years. Thus, the present study evaluated the effects of the aqueous extract of SZS (AESZS) on NicW-induced anxiety in male rats that received subcutaneous administrations of nicotine (Nic) (0.4 mg/kg, twice a day) for 7 d followed by 4 d of withdrawal. During NicW, the rats received four intragastric treatments of AESZS (60 mg/kg/d or 180 mg/kg/d). AESZS dose-dependently attenuated NicW-induced anxiety-like behaviors in the elevated plus maze (EPM) tests and 180 mg/kg/d AESZS inhibited NicW-induced increases in plasma corticosterone. Additionally, the protein and mRNA expressions of corticotropin-releasing factor (CRF) and CRF type 1 receptor (CRF1R) increased in the central nucleus of the amygdala (CeA) during NicW, but these changes were suppressed by 180 mg/kg/d AESZS. A post-AESZS infusion of CRF into the CeA abolished the attenuation of anxiety by AESZS and 180 mg/kg/d AESZS suppressed NicW-induced increases in norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the CeA. The present results suggest that AESZS ameliorated NicW-induced anxiety via improvements in CRF/CRF1R and noradrenergic signaling in the CeA.


2019 ◽  
Vol 484 (2) ◽  
pp. 228-232
Author(s):  
O. A. Deeva ◽  
A. S. Pantileev ◽  
I. V. Rybina ◽  
M. A. Yarkova ◽  
T. A. Gudasheva ◽  
...  

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.


2019 ◽  
Vol 33 (5) ◽  
pp. 640-646 ◽  
Author(s):  
Brian H Harvey ◽  
Wilmie Regenass ◽  
Walter Dreyer ◽  
Marisa Möller

Background: The chronobiotic antidepressant, agomelatine, acts via re-entrainment of circadian rhythms. Earlier work has demonstrated late-life anxiety and reduced corticosterone in post-weaning social isolation reared (SIR) rats. Agomelatine was anxiolytic in this model but did not reverse hypocortisolemia. Reduced corticosterone or cortisol (in humans) is well-described in anxiety states, although the anxiolytic-like actions of agomelatine may involve targeting another mechanism. Central oxytocin and vasopressin exert anxiolytic and anxiogenic effects, respectively, and are subject to circadian fluctuation, while also showing sex-dependent differences in response to various challenges. Aims and methods: If corticosterone is less involved in the anxiolytic-like actions of agomelatine in SIR rats, we wondered whether effects on vasopressin and oxytocin may mediate these actions, and whether sex-dependent effects are evident. Anxiety as assessed in the elevated plus maze, as well as plasma vasopressin, oxytocin, and corticosterone were analyzed in social vs SIR animals receiving sub-chronic treatment with vehicle or agomelatine (40 mg/kg/day intraperitoneally at 16:00) for 16 days. Results: Social isolation rearing induced significant anxiety together with increased plasma vasopressin levels, but decreased corticosterone and oxytocin. While corticosterone displayed sex-dependent changes, vasopressin, and oxytocin changes were independent of sex. Agomelatine suppressed anxiety as well as reversed elevated vasopressin in both male and female rats and partially reversed reduced oxytocin in female but not male rats. Conclusion: SIR-associated anxiety later in life involves reduced corticosterone and oxytocin, and elevated vasopressin. The anxiolytic-like effects of agomelatine in SIR rats predominantly involve targeting of elevated vasopressin.


2019 ◽  
Vol 168 (1) ◽  
pp. 52-54
Author(s):  
O. O. Masalova ◽  
S. B. Kazakova ◽  
T. N. Savateeva-Lyubimova ◽  
K. V. Sivak ◽  
N. S. Sapronov ◽  
...  

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

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.


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