scholarly journals Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2197 ◽  
Author(s):  
Alyssa Moore ◽  
Joshua Beidler ◽  
Mee Hong
Keyword(s):  
Side Effects ◽  
Animal Models ◽  
Treatment Options ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Japanese Knotweed ◽  
Biological Mechanisms ◽  
Swimming Test ◽  
Sucrose Preference Test ◽  
Higher Doses

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic–pituitary–adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10–80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.

scholarly journals Gut Microbiota Mediates the Preventive Effects of Dietary Capsaicin Against Depression-Like Behavior Induced by Lipopolysaccharide in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing Xia ◽  
Li Gu ◽  
Yitong Guo ◽  
Hongyan Feng ◽  
Shuhan Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Sequencing Analysis ◽  
Behavioral Indicators ◽  
16S Gene ◽  
Tnf Α ◽  
Antidepressant Effects ◽  
Swimming Test ◽  
Sucrose Preference Test

Capsaicin (CAP) is an active ingredient in chili pepper that is frequently consumed. It exerts various pharmacological activities, and also has potential effects on mental illness. However, its mechanism of antidepressant effects is still unclear. Based on the emerging perspective of the gut-brain axis, we investigated the effects of dietary CAP on gut microbes in mice with depression-like behaviors induced by lipopolysaccharide (LPS). C57BL/6J male mice (four weeks old) were given specific feed (standard laboratory chow or laboratory chow plus 0.005% CAP) for 4 months. During the last five days, LPS (0.052/0.104/0.208/0.415/0.83 mg/kg, 5-day) was injected intraperitoneally to induce depression. Behavioral indicators and serum parameters were measured, and gut microbiota were identified by sequencing analysis of the 16S gene. This study showed that dietary CAP improved depressive-like behavior (sucrose preference test, forced swimming test, tail suspension test) and levels of 5-HT and TNF-α in serum of LPS-induced mice with depression-like behaviors. In addition, CAP could recover abnormal changes in depression-related microbiota. Especially at the genus level, CAP enhanced the variations in relative abundance of certain pivotal microorganisms like Ruminococcus, Prevotella, Allobaculum, Sutterella, and Oscillospira. Correlation analysis revealed changes in microbiota composition that was closely related to depressive behavior, 5-HT and TNF-α levels. These results suggested that dietary CAP can regulate the structure and number of gut microbiota and play a major role in the prevention of depression.

scholarly journals Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yujin Choi ◽  
Yunna Kim ◽  
Hwa-Young Lee ◽  
Seung-Hun Cho
Keyword(s):  
Prefrontal Cortex ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Antidepressant Agent ◽  
Immobility Time ◽  
Swimming Test ◽  
Asian Pacific ◽  
Sucrose Preference Test ◽  
Tetragonia Tetragonioides

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

scholarly journals Antianhedonic and Antidepressant Effects of Affron®, a Standardized Saffron (Crocus Sativus L.) Extract

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3207
Author(s):  
Laura Orio ◽  
Francisco Alen ◽  
Antonio Ballesta ◽  
Raquel Martin ◽  
Raquel Gomez de Heras
Keyword(s):  
Bioactive Compounds ◽  
Forced Swimming Test ◽  
Preference Test ◽  
Forced Swimming ◽  
Crocus Sativus ◽  
Anxiety And Depression ◽  
Beneficial Role ◽  
Swimming Test ◽  
Sucrose Preference Test ◽  
Depressive States

Anxiety and depression have high prevalence in the general population, affecting millions of people worldwide, but there is still a need for effective and safe treatments. Nutritional supplements have recently received a lot of attention, particularly saffron. Thus, several pre-clinical studies support a beneficial role for bioactive compounds, such as saffron, in anxiety and depression. Here we used an animal model of depression based on social isolation to assess the effects of affron®, a standardized saffron extract containing ≥3.5% of total bioactive compounds safranal and crocin isomers. Affron® was administered both through the oral and the intraperitoneal routes, and several tasks related to anxiety and depression, such as the elevated plus maze, the forced swimming test or the sucrose preference test, were assessed. These tasks model key features of depressive states and anxious states relating to fear, behavioral despair or anhedonia, the lack of motivation and/or pleasure from everyday activities, respectively. Animals receiving oral affron® displayed behaviors congruent with improvements in their anxious/depressive state, showing the enhanced consumption of a sweet solution, as well as an increase in certain escape responses in the forced swimming test. Our data support a beneficial role for oral saffron in anxious/depressive states.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF TRANS-ANETHOLE IN UNSTRESSED MICE AND STRESSED MICE

2019 ◽  
pp. 121-127
Author(s):  
DINESH DHINGRA ◽  
SUDHA
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Monoamine Oxidase A ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Male Mice ◽  
Mao A ◽  
Sucrose Preference Test ◽  
Plasma Nitrite

Objectives: The present study was undertaken to investigate the antidepressant potential of trans-anethole in unstressed and stressed male mice. Methods: Swiss albino male mice were exposed to chronic unpredictable mild stress for 21 successive days. Simultaneously, trans-anethole (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) and fluoxetine (20 mg/kg) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. The effect of drugs on depressive-like behavior of mice was tested by tail suspension test (TST) and sucrose preference test. Results: Trans-anethole (25 mg/kg) and fluoxetine significantly decreased the immobility period of unstressed and stressed mice in TST as compared to their respective control. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. Trans-anethole did not show any significant effect on locomotor activity of mice. Antidepressant-like activity of trans-anethole (25 mg/kg) was found to be comparable to fluoxetine. Trans-anethole and fluoxetine significantly inhibited brain monoamine oxidase-A (MAO-A) activity, decreased plasma nitrite, brain malondialdehyde, and increased brain reduced glutathione levels and catalase activity in unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Conclusion: Trans-anethole produced significant antidepressant-like activity in unstressed and stressed mice, possibly through inhibition of brain MAO-A activity and alleviation of oxidative stress. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of trans-anethole in stressed mice.

scholarly journals A50 TRANSFER OF DEPRESSIVE-LIKE PHENOTYPE TO GNOTOBIOTIC MICE DEPENDS ON MICROBIAL FEATURES SPECIFIC TO INDIVIDUAL PATIENTS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 59-60
Author(s):  
J Hanuschak ◽  
M P Louis-Auguste ◽  
G De Palma ◽  
E Verdu ◽  
R Anglin ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Fecal Microbiota ◽  
Sucrose Preference ◽  
Rrna Gene ◽  
Fecal Microbiota Transplant ◽  
Total N ◽  
Significant Difference ◽  
Sucrose Preference Test

Abstract Background Major depressive disorder (MDD) affects approximately 4.4% of the global population. Despite its high prevalence, little is known about the mechanisms underlying this disorder. Recent studies in both humans and rodents have suggested that the intestinal microbiota may play a role in depression. Altered microbiota composition has been found in a subset of MDD patients. Preclinical studies have suggested that fecal microbiota transplant using pooled MDD patient samples can induce depressive-like behaviour in rodents. We have previously shown that the use of different microbiota donors with irritable bowel syndrome results in the induction of different phenotypes in recipient mice. Thus, we have hypothesized that pooling microbiota samples abrogates features that are unique to individual donors. Aims (1) Investigate whether the transfer of individual MDD patient microbiota can induce depressive-like behaviour in germ-free (GF) mice (2) Identify features of individual MDD patient microbiota that are associated with the depressive-like phenotype Methods GF NIH Swiss mice of both sexes (min. n=10 per group, total n=110) were colonized with either fecal microbiota from a single donor, MDD patient (MDD1-4) or matched healthy control (HC1-4), or pooled fecal microbiota from MDD1-4 or HC1-4. Mouse behaviour was assessed, using the open field test, three chamber sociability assay, tail suspension test, and sucrose preference test. Stool samples were collected throughout the experiment for 16S rRNA gene sequencing. Results Mice colonized with microbiota from patient MDD1 exhibited depressive-like behaviour, as assessed by the sucrose preference test and sociability assay, when compared to mice colonized with HC1 microbiota. This was not true for mice colonized with individual microbiota from the other three patients (MDD2-4) or with pooled MDD microbiota. Comparative analysis of the 16S data revealed a significant difference in Faith’s Phylogenetic Diversity between MDD1 microbiota and pooled MDD microbiota. Four bacterial species were found to be significantly associated with the depressive-like phenotype in mice: Bacteroides acidifaciens, Bacteroides ovatus, unclassified species of Phascolarctobacterium (Veillonellacae family), and Eggerthella lenta. The relative abundances of these species did not differ significantly between the two pooled groups. Conclusions Microbiota from some, but not all, MDD patients can induce a depressive-like phenotype in GF mice. The ability to induce depressive-like behaviour in GF mice is lost when microbiota from multiple patients is pooled. Specific bacterial species may be responsible for the successful transfer of the depressive-like phenotype to mice. Funding Agencies NIH

scholarly journals Enhanced Antidepressant-Like Effects of Electroacupuncture Combined with Citalopram in a Rat Model of Depression

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jian Yang ◽  
Yu Pei ◽  
Yan-Li Pan ◽  
Jun Jia ◽  
Chen Shi ◽  
...  
Keyword(s):  
Side Effects ◽  
Depressive Disorders ◽  
Low Dose ◽  
Combined Treatment ◽  
Preference Test ◽  
Vehicle Group ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Antidepressant Efficacy ◽  
Sucrose Preference Test

Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.

Repeated ketamine administration redeems the time lag for citalopram's antidepressant-like effects

2015 ◽  
Vol 30 (4) ◽  
pp. 504-510 ◽  
Author(s):  
G.-F. Zhang ◽  
W.-X. Liu ◽  
L.-L. Qiu ◽  
J. Guo ◽  
X.-M. Wang ◽  
...  
Keyword(s):  
Remission Rate ◽  
Time Lag ◽  
Onset Time ◽  
Preference Test ◽  
Mild Stress ◽  
Once Daily ◽  
Treatment Regimens ◽  
Antidepressant Effects ◽  
Swimming Test ◽  
Sucrose Preference Test

AbstractCurrent available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.

scholarly journals P2Y12 receptor as a new target for electroacupuncture relieving comorbidity of visceral pain and depression of inflammatory bowel disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanzhen Li ◽  
Hong Zhang ◽  
Jingwen Yang ◽  
Muouyang Zhan ◽  
Xuefei Hu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Visceral Pain ◽  
Preference Test ◽  
Tail Suspension Test ◽  
P2y12 Receptor ◽  
Trinitrobenzene Sulfonic Acid ◽  
P2y12 Inhibitors ◽  
Inflammatory Bowel ◽  
Sucrose Preference Test

Abstract Background The P2Y12 receptor is a kind of purinoceptor that is engaged in platelet aggregation, and P2Y12 inhibitors have been used in clinical antithrombotic therapy. The P2Y12 receptor in microglia induces interleukin-1β (IL-1β) expression, which is a key mediator of depression in the brain. Although peripheral P2Y12 is involved in neuropathic pain, whether P2Y12 expression in the medial prefrontal cortex (mPFC) is associated with comorbidities of visceral pain and depression remains unclear. Accumulating evidence suggests that electroacupuncture (EA) is effective in treating inflammatory bowel disease (IBD), but its mechanism is unknown. This study aimed to determine whether P2Y12 expression in the mPFC is associated with comorbidities of visceral pain and depression in IBD and whether EA treats IBD by targeting the P2Y12 receptor. Methods We used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD mice. P2Y12 short hairpin RNA (shRNA) was stereotaxically injected into the bilateral mPFC. EA was performed on bilateral “Dachangshu” (BL25) acupoints once a day for 7 days. Von Frey filaments and colorectal distension were used to detect the mechanical pain threshold and visceral pain sensitivity. The sucrose preference test, tail suspension test and forced swimming test were used to evaluate depression in mice. Western blotting was used to test the expression of P2Y12 and IL-1β. Immunofluorescence staining was used to assess microglial activity. Results We found that IBD mice presented visceral pain and depression associated with increased P2Y12 expression in the mPFC. P2Y12 shRNA significantly attenuated visceral pain and depression in IBD mice. P2Y12 shRNA significantly downregulated IL-1β expression and inhibited the activation of microglia in the mPFC of IBD mice. Meanwhile, EA played a similar role of P2Y12 shRNA. EA significantly downregulated P2Y12 expression, weakened the activation of microglia, and then inhibited IL-1β expression in the mPFC, thus relieving visceral pain and depression in IBD mice. Conclusion The present study provided new ideas that the P2Y12 receptor in the mPFC could be a new target for the treatment of comorbid visceral pain and depression by EA. This may not only deepen our understanding of the analgesic and antidepressant mechanisms of EA but also promote the application of EA to treat IBD.

scholarly journals Using tests and models to assess antidepressant-like activity in rodents

2016 ◽  
Vol 29 (2) ◽  
pp. 61-65 ◽  
Author(s):  
Ewa Kedzierska ◽  
Izabela Wach
Keyword(s):  
Animal Models ◽  
Learned Helplessness ◽  
Forced Swimming Test ◽  
Chronic Mild Stress ◽  
Tail Suspension Test ◽  
Depression Treatment ◽  
Mild Stress ◽  
Animal Models Of Depression ◽  
Important Challenge ◽  
Swimming Test

Abstract In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.

scholarly journals VEGF Treatment Ameliorates Depression-Like Behavior in Adult Offspring after Maternal Immune Activation

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1048
Author(s):  
Spyridon Sideromenos ◽  
Claudia Lindtner ◽  
Alice Zambon ◽  
Orsolya Horvath ◽  
Angelika Berger ◽  
...  
Keyword(s):  
Immune Activation ◽  
Therapeutic Potential ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Vegf Receptor ◽  
Maternal Immune Activation ◽  
Extracellular Signal ◽  
Sucrose Preference Test ◽  
And Behavior ◽  
Endothelial Growth Factor

Maternal immune activation (MIA) during pregnancy impacts offspring neurodevelopmental trajectories and induces lifelong consequences, including emotional and cognitive alterations. Using the polyinosinic:polycytidilic acid (PIC) MIA model we have previously demonstrated enhanced depression-like behavior in adult MIA offspring, which was associated with reduced expression of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) in the hippocampus. Since VEGF mediates the effects of various antidepressant agents, we here set out to explore whether VEGF administration could rescue the depression-like behavioral deficits in MIA offspring. To test our hypothesis, control and MIA offspring were intracerebroventricularly (i.c.v.) infused with either VEGF or vehicle solution and depression-related behavior was assessed in the sucrose preference test (SPT) and the tail suspension test (TST). As a surrogate of VEGF activity, the phosphorylation of the extracellular signal-regulated kinase (ERK) in hippocampus was quantified. We found that VEGF treatment reduced depression-related behavioral despair in the TST in MIA offspring but had no effect on anhedonia-like behavior in the SPT. While VEGF administration induced the phosphorylation of ERK in the hippocampus of control offspring, this effect was blunted in the MIA offspring. We conclude that VEGF administration, at the dosage tested, beneficially affects some aspects of the depression-like phenotype in the adult MIA offspring, inviting further studies using different dosage regimes to further explore the therapeutic potential of VEGF treatment in MIA-related changes in brain function and behavior.

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