scholarly journals Dapoxetine: An Innovative Approach in the Therapeutic Management In Animal Model of Depression

2016 ◽  
Vol 2 (1) ◽  
pp. 15
Author(s):  
Hira Rafi ◽  
Muhammad Farhan
Keyword(s):  
Learned Helplessness ◽  
Chronic Mild Stress ◽  
Repeated Administration ◽  
Mild Stress ◽  
Behavioral Deficits ◽  
Unpredictable Chronic Mild Stress ◽  
Field Environment ◽  
Novel Approach ◽  
Synaptic Receptors ◽  
Familiar Environment

Stress is a complicated condition that effects on person’s mental and physical health, and it is the precursor of other psychological disorders mainly depression. Serotonin (5-Hydroxytryptamine; 5-HT) is well known to have hypofunction in unpredictable chronic mild stress whereas, unpredictable chronic mild stress (UCMS) has produced the most steady and continuous results of anhedonia and learned helplessness particularly in rats. The stress-induced depressive like behavior can be reversed by many antidepressants such as SSRIs. Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) is mostly prescribed antidepressant that can deplete neurochemical and behavioral deficits. The present study was designed to investigate whether repeated administration of dapoxetine at dose (1.0 mg/kg) could reverse the behavioral deficits induced by UCMS in rat model of depression. UCMS induced behavioral deficits. Locomotor  activity in familiar environment (home cage), novel (open field) environment and anxiolytic behavior in light/dark activity box were greater in unstressed group than stressed group. The inhibition of serotonin reuptake at pre-synaptic receptors by repeated dapoxetine administration is mainly the mechanism involved and discussed. This particular study may assist in novel approach for understanding the interaction between stress and behavioral functions and extending the therapeutic use of dapoxetine.

scholarly journals Prophylactic efficacy of riluzole against anxiety- and depressive-like behaviors in two rodent stress models

2020 ◽  
Author(s):  
Corey Fee ◽  
Keith A. Misquitta ◽  
Etienne Sibille ◽  
Robert M. Berman ◽  
Vladimir Coric ◽  
...  
Keyword(s):  
Traumatic Stress ◽  
Learned Helplessness ◽  
Prophylactic Treatment ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Post Traumatic Stress ◽  
Major Depressive ◽  
Behavioral Deficits ◽  
Unpredictable Chronic Mild Stress ◽  
Post Traumatic

AbstractBackgroundChronic stress-related illnesses, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), share symptomatology, including anxiety, anhedonia, and helplessness. Across disorders, neurotoxic dysregulated glutamate (Glu) signaling may underlie symptom emergence. Current first-line antidepressant drugs (ADs), which do not directly target Glu signaling, fail to provide adequate benefit for many patients and are associated with high relapse rates. Riluzole modulates glutamatergic neurotransmission by increasing metabolic cycling and modulating signal transduction. Clinical studies exploring riluzole’s efficacy in stress-related disorders have provided varied results. However, the utility of riluzole for treating specific symptom dimensions or as a prophylactic treatment has not been comprehensively assessed.MethodsWe investigated whether chronic prophylactic riluzole (∼12-15/kg/day p.o.) could prevent the emergence of behavioral deficits induced by unpredictable chronic mild stress (UCMS) in mice. We assessed i) anxiety-like behavior using the elevated-plus maze, open field test, and novelty-suppressed feeding, ii) mixed anxiety/anhedonia-like behavior in the novelty-induced hypophagia test and, iii) anhedonia-like behavior using the sucrose consumption test. Z-scoring summarized changes across tests measuring similar outcomes. In a separate learned helplessness (LH) cohort, we investigated whether chronic preventative riluzole treatment could block the development of helplessness-like behavior.ResultsUCMS induced an elevation in anxiety-, anhedonia-like behavior, and overall behavioral emotionality that was blocked by prophylactic riluzole. In the LH cohort, preventative riluzole blocked the development of helplessness-like behavior.ConclusionThis study supports the utility of riluzole as a prophylactic medication, and potential relapse-preventing treatment targeting anhedonia, anxiety, and helplessness symptoms associated with stress-related disorders.Significance StatementRiluzole is a glutamate-modulating drug with mixed evidence of efficacy in clinical studies of patients with stress-related disorders. Based on evidence suggesting that glutamatergic dysfunction contributes to the pathogenesis of stress-related disorders, we investigated whether prophylactic treatment with riluzole could prevent the onset of behavioral deficits induced by unpredictable chronic mild stress or learned helplessness in mice. Riluzole effectively prevented the emergence of anxiety-, anhedonia-like behavior, and overall behavioral emotionality in mice exposed to unpredictable chronic mild stress. In a separate cohort, riluzole blocked the emergence of helplessness-like behavior as measured in an active avoidance paradigm. These results support testing riluzole as a prophylactic treatment strategy in stress-related illnesses such as major depressive disorder or post-traumatic stress disorder.

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 Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20955 ◽  
Author(s):  
Xian-cang Ma ◽  
Dong Jiang ◽  
Wen-hui Jiang ◽  
Fen Wang ◽  
Min Jia ◽  
...  
Keyword(s):  
Social Isolation ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Male Mice ◽  
Unpredictable Chronic Mild Stress

scholarly journals Telmisartan Activates PPARδ to Improve Symptoms of Unpredictable Chronic Mild Stress-Induced Depression in Mice

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yingxiao Li ◽  
Kai-Chun Cheng ◽  
Keng-Fan Liu ◽  
Wen-Huang Peng ◽  
Juei-Tang Cheng ◽  
...  
Keyword(s):  
Chronic Mild Stress ◽  
Mild Stress ◽  
Unpredictable Chronic Mild Stress
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