Antidepressant-like effects of a novel 5-HT3 receptor antagonist 6z in acute and chronic murine models of depression

Gupta, Deepali; Mahesh, Radhakrishnan; Kurhe, Yeshwant; Devadoss, Thangaraj; Prabhakar, Visakh; Kanade, Prateek

doi:10.1038/aps.2014.89

Cited by 26 publications

(11 citation statements)

References 52 publications

(108 reference statements)

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“…Free radicals at high concentration levels in the human body can cause oxidative stress, thus destroying internal redox balance and causing a variety of chronic diseases [83, 84]. …”

Section: Oxidative Stressmentioning

confidence: 99%

“…During the metabolic process, free radicals are produced in the human body, causing oxidation in biological macromolecules such as proteins, fatty acids, and nucleic acids. Free radicals at high concentration levels in the human body can cause oxidative stress, thus destroying internal redox balance and causing a variety of chronic diseases [ 83 , 84 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

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Mangiferin: a natural miracle bioactive compound against lifestyle related disorders

et al. 2017

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The current review article is an attempt to explain the therapeutic potential of mangiferin, a bioactive compound of the mango, against lifestyle-related disorders. Mangiferin (2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one) can be isolated from higher plants as well as the mango fruit and their byproducts (i.e. peel, seed, and kernel). It possesses several health endorsing properties such as antioxidant, antimicrobial, antidiabetic, antiallergic, anticancer, hypocholesterolemic, and immunomodulatory. It suppresses the activation of peroxisome proliferator activated receptor isoforms by changing the transcription process. Mangiferin protects against different human cancers, including lung, colon, breast, and neuronal cancers, through the suppression of tumor necrosis factor α expression, inducible nitric oxide synthase potential, and proliferation and induction of apoptosis. It also protects against neural and breast cancers by suppressing the expression of matrix metalloproteinase (MMP)-9 and MMP-7 and inhibiting enzymatic activity, metastatic potential, and activation of the β-catenin pathway. It has the capacity to block lipid peroxidation, in order to provide a shielding effect against physiological threats. Additionally, mangiferin enhances the capacity of the monocyte-macrophage system and possesses antibacterial activity against gram-positive and gram-negative bacteria. This review summarizes the literature pertaining to mangiferin and its associated health claims.

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“…Free radicals at high concentration levels in the human body can cause oxidative stress, thus destroying internal redox balance and causing a variety of chronic diseases [83, 84]. …”

Section: Oxidative Stressmentioning

confidence: 99%

Section: Oxidative Stressmentioning

confidence: 99%

Mangiferin: a natural miracle bioactive compound against lifestyle related disorders

et al. 2017

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“…The UCMS model includes chronic depression by presenting unpredictable stress stimuli (Gupta et al, ) such as multiple, randomly scheduled food and water deprivation, overnight illumination, cage tilting, and other similar stressors that may be associated with human patients (Boyle et al, ). In most published studies, the UCMS model induced depression for 2–4 weeks, but some have been tested for up to eight weeks (He et al, ; Wu et al, ; Xia et al, ; Yan et al, ; N. Zhang et al, ).…”

Section: Introductionmentioning

confidence: 99%

Long‐term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression

et al. 2019

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Objective:The present study was designed to explore the long-term differences between three mouse models for depression. Method:In the present study, the unpredictable chronic mild stress (UCMS) model, the glucocorticoid/corticosterone model, and the olfactory bulbectomy model were compared at two, three, and five weeks after model induction. Behavioral testing performed included forced-swimming, tail suspension, open-field and elevated plusmaze tests. In addition, 5-hydroxytryptamine (5-HT) and dopamine levels, and mRNA and protein expressions related to 5-HT synthesis, transport, and signaling were analyzed in the hippocampus of tested animals. Results:Our results revealed that each model demonstrated a specific profile of markers, whereas the stability of them differed over testing time. Conclusions:Each model provided a unique set of advantages that can be considered depending on the context and aims of each study. Among the three models, the UCMS model was mostly stable and appeared to the best model for testing long-term depression-like state. K E Y W O R D S 5-HT, corticosterone, depression model, glucocorticoid, olfactory bulbectomy, UCMS How to cite this article: Zhu H, Tao Y, Wang T, et al. Long-term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression. Brain Behav. 2020;10:e01508. https ://doi.

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“…Functional antagonism of the antidepressants on 5-HT 3 receptor was reported in previous studies [ 21 27 42 ]. Also ondansetron was known to improve a mood disturbance in the depressive patients and reduce anxiety behaviors in the mice models of depression [ 41 43 44 45 ]. Although these reports suggest the important role of 5-HT 3 receptor in the depressive disorders, few antidepressants have been studied to test whether they modulated this receptor directly.…”

Section: Discussionmentioning

confidence: 99%

Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

Park

Myeong

Kim

et al. 2018

Korean J Physiol Pharmacol

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Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 (5-HT3) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with 5-HT3 receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the 5-HT3 receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express 5-HT3 receptors. To elucidate the mechanism of amitriptyline, we simulated the 5-HT3 receptor currents using Berkeley Madonna® software and calculated the rate constants of the agonist binding and receptor transition steps. The 5-HT3 receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the 5-HT3 receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the 5-HT3 receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a 5-HT3 receptor, a potential target of neurologic and psychiatric diseases through this study.

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Antidepressant-like effects of a novel 5-HT3 receptor antagonist 6z in acute and chronic murine models of depression

Abstract: 6z is a novel 5-HT3 receptor antagonist with potential antidepressant-like activities, which may be related to modulating hypothalamic-pituitary-adrenal axis and attenuating brain oxidative damage.

Cited by 26 publications

References 52 publications

Mangiferin: a natural miracle bioactive compound against lifestyle related disorders

Mangiferin: a natural miracle bioactive compound against lifestyle related disorders

Long‐term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression

Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

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