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 Increased Neuronal DNA/RNA Oxidation in the Frontal Cortex of Mice Subjected to Unpredictable Chronic Mild Stress

2017 ◽  
Vol 1 ◽  
pp. 247054701772474 ◽  
Author(s):  
Alfred M. Maluach ◽  
Keith A. Misquitta ◽  
Thomas D. Prevot ◽  
Corey Fee ◽  
Etienne Sibille ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Frontal Cortex ◽  
Chronic Stress ◽  
Basolateral Amygdala ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Major Depressive ◽  
Unpredictable Chronic Mild Stress ◽  
Rna Oxidation

Background Chronic stress is implicated in the development of various psychiatric illnesses including major depressive disorder. Previous reports suggest that patients with major depressive disorder have increased levels of oxidative stress, including higher levels of DNA/RNA oxidation found in postmortem studies, especially within brain regions responsible for the cognitive and emotional processes disrupted in the disorder. Here, we aimed to investigate whether unpredictable chronic mild stress in mice induces neuronal DNA/RNA oxidation in the prelimbic, infralimbic, and cingulate cortices of the frontal cortex and the basolateral amygdala and to explore potential associations with depressive-like behaviors. We expected that animals subjected to unpredictable chronic mild stress will present higher levels of DNA/RNA oxidation, which will be associated with anxiety-/depressive-like behaviors. Methods C57BL/6J mice were assigned to unpredictable chronic mild stress or nonstress conditions (n = 10/group, 50% females). Following five weeks of unpredictable chronic mild stress exposure, mice were tested in a series of behavioral tests measuring anxiety- and depressive-like behaviors. Frontal cortex and amygdala sections were then immunolabeled for neuronal nuclei, a marker of post-mitotic neurons and anti-8-hydroxy-2-deoxyguanosine/8-oxo-7,8-dihydroguanosine, which reflects both DNA and RNA oxidation. Results Levels of neuronal DNA/RNA oxidation were increased in the frontal cortex of mice subjected to unpredictable chronic mild stress ( p = 0.0207). Levels of neuronal DNA/RNA oxidation in the frontal cortex were positively correlated with z-emotionality scores for latency to feed in the novelty-suppressed feeding test ( p = 0.0031). Statistically significant differences were not detected in basolateral amygdala levels of neuronal DNA/RNA oxidation between nonstress- and unpredictable chronic mild stress-exposed mice, nor were correlations found with behavioral performances for this region. Conclusion Our results demonstrate that unpredictable chronic mild stress induces a significant increase in neuronal DNA/RNA oxidation in the frontal cortex that correlate with behavioral readouts of the stress response. A lack of DNA/RNA oxidation alterations in the basolateral amygdala suggests greater vulnerability of frontal cortex neurons to DNA/RNA oxidation in response to unpredictable chronic mild stress. These findings add support to the hypothesis that chronic stress-induced damage to DNA/RNA may be an additional molecular mechanism underlying cellular dysfunctions associated with chronic stress and present in stress-related disorders.

scholarly journals CRF-R1 Antagonist Treatment Exacerbates Circadian Corticosterone Secretion under Chronic Stress, but Preserves HPA Feedback Sensitivity

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2114
Author(s):  
Yadira Ibarguen-Vargas ◽  
Samuel Leman ◽  
Rupert Palme ◽  
Catherine Belzung ◽  
Alexandre Surget
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Chronic Mild Stress ◽  
Stress Conditions ◽  
Mild Stress ◽  
Circadian Activity ◽  
Corticosterone Secretion ◽  
Feedback Sensitivity ◽  
The Impact

Despite promising initial reports, corticotropin-releasing factor receptor type-1 (CRF-R1) antagonists have mostly failed to display efficacy in clinical trials for anxiety or depression. Rather than broad-spectrum antidepressant/anxiolytic-like drugs, they may represent an ‘antistress’ solution for single stressful situations or for patients with chronic stress conditions. However, the impact of prolonged CRF-R1 antagonist treatments on the hypothalamic–pituitary–adrenal (HPA) axis under chronic stress conditions remained to be characterized. Hence, our study investigated whether a chronic CRF-R1 antagonist (crinecerfont, formerly known as SSR125543, 20 mg·kg−1·day−1 ip, 5 weeks) would alter HPA axis basal circadian activity and negative feedback sensitivity in mice exposed to either control or chronic stress conditions (unpredictable chronic mild stress, UCMS, 7 weeks), through measures of fecal corticosterone metabolites, plasma corticosterone, and dexamethasone suppression test. Despite preserving HPA axis parameters in control non-stressed mice, the 5-week crinercerfont treatment improved the negative feedback sensitivity in chronically stressed mice, but paradoxically exacerbated their basal corticosterone secretion nearly all along the circadian cycle. The capacity of chronic CRF-R1 antagonists to improve the HPA negative feedback in UCMS argues in favor of a potential therapeutic benefit against stress-related conditions. However, the treatment-related overactivation of HPA circadian activity in UCMS raise questions about possible physiological outcomes with long-standing treatments under ongoing chronic stress.

scholarly journals Environmental Enrichment Ameliorates Anxiety-Like Behavior in Rats without Altering Plasma Corticosterone Level

2021 ◽  
Vol 9 (A) ◽  
pp. 1074-1080
Author(s):  
Muthmainah Muthmainah ◽  
Winda Atika Sari ◽  
Nanang Wiyono ◽  
Dhoni Akbar Ghazali ◽  
Ratih Dewi Yudhani ◽  
...  
Keyword(s):  
Environmental Enrichment ◽  
Corticosterone Level ◽  
Anxiolytic Effect ◽  
Chronic Mild Stress ◽  
Plasma Corticosterone ◽  
Mild Stress ◽  
Environmental Interventions ◽  
Behavioral Measurement ◽  
Plus Maze ◽  
And Function

BACKGROUND: Anxiety disorder is one of the most common psychiatric problems. Prolonged stress gives rise to anxiety-like behavior in animals. Environmental interventions influence the outcome of anxiety treatment. Environmental enrichment (EE) can modulate brain’s structure and function. AIM: The objective of the study was to evaluate EE effects on anxiety-like behavior and corticosterone (CORT) level after unpredictable chronic mild stress (UCMS). METHODS: A total of 28 rats were assigned into four groups randomly: Control, UCMS, UCMS+EE, and UCMS+fluoxetine. UCMS, EE, and fluoxetine were given for 21 days. Anxiety behavior was measured on day 22nd using Elevated Plus Maze. Behavioral measurement was based on the total time spent and total entries onto open and closed arms. CORT was measured using ELISA. RESULTS: UCMS increased anxiety-like behavior as seen from reduced number of entries and time spent in open arms as well as increased number of entries and time spent in in closed arms in UCMS group than control. Rats in EE group spent more time and made more entries in the open arms than UCMS group (both p = 0.002). Anxiolytic effect of EE was stronger than fluoxetine. Plasma CORT level among groups did not differ significantly (p = 0.351). CONCLUSION: EE can ameliorate stress-induced anxiety-like behavior without affecting CORT level.

scholarly journals Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

2021 ◽  
Vol 14 (7) ◽  
pp. 659
Author(s):  
Juthamart Maneenet ◽  
Orawan Monthakantirat ◽  
Supawadee Daodee ◽  
Chantana Boonyarat ◽  
Yutthana Chotritthirong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Chronic Mild Stress ◽  
Antidepressant Activity ◽  
Piper Nigrum ◽  
Psychiatric Disease ◽  
Mild Stress ◽  
Herbal Formula ◽  
Necrosis Factor Alpha ◽  
Unpredictable Chronic Mild Stress

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

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 Effects of Simultaneous Reinforcement of Endocannabinoid and Cholinergic Systems on Anxiety-Like Behavior in Mice

2021 ◽  
Author(s):  
Siamak Shahidi ◽  
Asghar Dindar ◽  
Alireza Komaki ◽  
Reihaneh Sadeghian
Keyword(s):  
Elevated Plus Maze ◽  
Enzyme Inhibitor ◽  
Endocannabinoid System ◽  
Anxiolytic Effect ◽  
Control Group ◽  
Concurrent Administration ◽  
Elevated Plus Maze Test ◽  
Cholinergic Systems ◽  
Plus Maze ◽  
High Doses

Abstract ObjectiveAnxiety behavior is regulated by different neurotransmitter systems. There has been no direct relationship between endocannabinoid and cholinergic systems on anxiety in previous studies. This study investigated the effects of each of these systems separately and simultaneously using Donepezil (Cholinesterase inhibitor) and URB-597 (endocannabinoid degrading enzyme inhibitor) on anxiety-like behavior. MethodEighty-eight male mice were divided into eleven groups (n=8) including control (saline), diazepam (0.3 mg /kg), URB-597 (0.1, 0.3, or 1 mg /kg), donepezil (0.5, 1 or 2 mg/kg) and the combination of the two drugs at low, medium and high doses. All treatments were injected intraperitoneally 30 minutes before the elevated plus maze test. ResultsSeparate administration of URB597, donepezil or diazepam increased the number and time spent of open arms compared to the control group. Concurrent administration of URB and donepezil at low, medium and high doses did not change the number of open arms entries compared to the control group, but they reduced the number of entries to the closed arms. ConclusionsThese results suggest that strengthening any cholinergic or endocannabinoid system has anxiolytic effect similar to diazepam. However, the interaction of these two systems has fewer anxiolytic effects compared to the effects of each alone. It seems that these drugs alone may represent a strategy for the treatment of anxiety disorders.

Sign in / Sign up

Export Citation Format

Share Document