Involvement of oxidative pathways and BDNF in the antidepressant effect of carvedilol in a depression model induced by chronic unpredictable stress

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234)), resulting in an increased pGR(S220/S234) ratio. We also observed negative correlations between pGR(S220)/(S234) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.

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Antidepressant effect of venlafaxine in chronic unpredictable stress: Evidence of the involvement of key enzymes responsible for monoamine neurotransmitter synthesis and metabolism

Molecular Medicine Reports ◽

10.3892/mmr.2019.10489 ◽

2019 ◽

Author(s):

Dan Liu ◽

Xiao‑Ya Hu ◽

Hai‑Jian Xia ◽

Li‑Jia Wang ◽

Ping Shi ◽

...

Keyword(s):

Antidepressant Effect ◽

Monoamine Neurotransmitter ◽

Chronic Unpredictable Stress ◽

Key Enzymes ◽

Neurotransmitter Synthesis

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The Faster-Onset Antidepressant Effects of Hypidone Hydrochloride (YL-0919) in Monkeys Subjected to Chronic Unpredictable Stress

Frontiers in Pharmacology ◽

10.3389/fphar.2020.586879 ◽

2020 ◽

Vol 11 ◽

Author(s):

Yong-Yu Yin ◽

Chao-Yang Tian ◽

Xin-Xin Fang ◽

Chao Shang ◽

Li-Ming Zhang ◽

...

Keyword(s):

Social Status ◽

Antidepressant Drugs ◽

Onset Time ◽

Antidepressant Effect ◽

Chronic Unpredictable Stress ◽

Once Daily ◽

Cynomolgus Monkeys ◽

Monkey Model ◽

Antidepressant Effects ◽

Significant Depression

Given the limited monkey models of depression available to date, as well as the procedural complexity and time investments that they involve, the ability to test the efficacy and time course of antidepressants in monkey models is greatly restricted. The present study attempted to build a simple and feasible monkey model of depression with chronic unpredictable stress (CUS) and evaluate the antidepressant effect and onset time of fluoxetine hydrochloride (FLX) and the new drug hypidone hydrochloride (YL-0919), a potent and selective 5-HT reuptake inhibitor, 5-HT1A receptor partial agonist and 5-HT6 receptor full agonist. Female cynomolgus monkeys with low social status in their colonies were selected and subjected to CUS for 8 weeks by means of food and water deprivation, space restriction, loud noise, strobe light, and intimidation with fake snakes. Huddling, self-clasping, locomotion and environmental exploration were monitored to evaluate behavioral changes. In addition, the window-opening test was used to evaluate the exploratory interest of the monkeys. The present results revealed that CUS-exposed monkeys displayed significant depression-like behaviors, including significant decreases in exploratory interest, locomotion, and exploration as well as significant increases in huddling and self-clasping behavior and the level of fecal cortisol after 8 weeks of CUS. Treatment with FLX (2.4 mg/kg, i. g.) or YL-0919 (1.2 mg/kg, i. g.) markedly reversed the depression-like behaviors caused by CUS, producing significant antidepressant effects. YL-0919 (once daily for 9 days) had a faster-onset antidepressant effect, compared with FLX (once daily for 17 days). In summary, the present study first established a CUS model using female cynomolgus monkeys with low social status and then successfully evaluated the onset time of 5-HTergic antidepressants. The results suggested that monkeys exposed to CUS displayed significant depression-like behaviors, and both FLX and YL-0919 produced antidepressant effects in this model. Moreover, YL-0919 appeared to act faster than FLX. The present study provides a promising prospect for the evaluation of fast-onset antidepressant drugs based on a CUS monkey model.

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Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure

Behavioural Neurology ◽

10.1155/2021/6651492 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

A. R. Tejeda-Martínez ◽

J. M. Viveros-Paredes ◽

G. V. Hidalgo-Franco ◽

E. Pardo-González ◽

V. Chaparro-Huerta ◽

...

Keyword(s):

Oxidative Stress ◽

Dentate Gyrus ◽

Depressive Disorders ◽

Adrenal Glands ◽

Enzyme Inhibitor ◽

Acid Amide ◽

Relative Weight ◽

Antidepressant Effect ◽

Chronic Unpredictable Stress ◽

Neural Precursors

Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.

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Antidepressant Activity of Alpha-lactalbumin in Chronic Unpredictable Stress Model in Swiss Albino Mice

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4315 ◽

2020 ◽

Vol 8 (A) ◽

pp. 93-99

Author(s):

Gihan F. Asaad ◽

Rania F. Ahmed ◽

Somaia A. Nada ◽

Ezz El-Din S. Eldenshary ◽

Nadia M. S. Arafa ◽

...

Keyword(s):

Whey Protein ◽

Antidepressant Activity ◽

Essential Amino Acids ◽

Antidepressant Effect ◽

Depression Symptoms ◽

Chronic Unpredictable Stress ◽

Monoamine Neurotransmitters ◽

Major Depressive ◽

Protein Components ◽

Alpha Lactalbumin

BACKGROUND: Major depressive disorder (MDD) is a leading cause for morbidity and mortality. Whey protein components are recently used as functional foods with health benefits. Alpha-lactalbumin (A-LA) is an important component of whey protein. It is a good source of the essential amino acids. OBJECTIVE: This study aimed to examine the possible antidepressant effect of whey protein against MDD induced by chronic unpredictable stress (CUS) in mice. MATERIALS AND METHODS: CUS model is used to induce depression in mice for 24 consecutive days and aimed to evaluate the ability of A-LA compared to fluoxetine to recover depression symptoms. Thirty minutes before exposure to the physical stressor, mice were given A-LA daily in a dose of 75, 150, and 300 mg/kg bwt. RESULTS: The highest dose of A-LA (300 mg/kg bwt.) lessens depression induced in mice. CONCLUSION: This effect might contribute to elevate the level of glutamate and monoamine neurotransmitters, γ-amino-butyric acid inhibition, and enhancement of glutathione in brain tissue.

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Sini Tang Prevents Depression-Like Behavior in Rats Exposed to Chronic Unpredictable Stress

The American Journal of Chinese Medicine ◽

10.1142/s0192415x0900693x ◽

2009 ◽

Vol 37 (02) ◽

pp. 261-272 ◽

Cited By ~ 17

Author(s):

Jian-You Guo ◽

Hai-Ru Huo ◽

Lan-Fang Li ◽

Shu-Ying Guo ◽

Ting-Liang Jiang

Keyword(s):

Open Field ◽

Corticosterone Level ◽

Sucrose Preference ◽

Antidepressant Effect ◽

Depression Symptoms ◽

Dependent Manner ◽

Chronic Unpredictable Stress ◽

Reverse Transcription Pcr ◽

Dose Dependent ◽

The Brain

Sini Tang, a Chinese traditional prescription containing three herbs, has been widely used for Yang-deficiency. Recent clinical studies have shown that Sini Tang could treat and improve depression symptoms, but the mechanisms underlying the antidepressant effect of Sini Tang remains unknown. In rats with chronic unpredictable stress (CUS), we examined the effects of Sini Tang on sucrose preference and open field exploratory behavior. The levels of corticosterone level in plasma and corticotropin- releasing hormone (CRH) mRNA expression in hypothalamus were also measured by enzyme-linked immunosorbent assays (ELISA) and real-time reverse transcription PCR (RT-PCR), respectively. Rats subjected to CUS exhibited decreases in sucrose preference and ambulation in the open field test. These were all attenuated by Sini Tang in a dose-dependent manner. Biochemically, Sini Tang also reversed CUS-induced increases in corticosterone in plasma and CRH mRNA in the hypothalamus. The behavioral effects of the Sini Tang were correlated to the biochemical actions. These results suggest that Sini Tang produces an antidepressant-like effect, which appears to involve CRH in the brain.

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