Neuropharmacological evaluation of a novel 5-HT<sub>3</sub> receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice

Bhatt, Shvetank; Mahesh, Radhakrishnan; Devadoss, Thangaraj; Jindal, Ankur

doi:10.1515/jbcpp-2016-0083

Cited by 16 publications

(10 citation statements)

References 27 publications

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“…This increase in depressive-like behavior was also seen in the sucrose preference test when using an LPS dose of 0.83 mg/kg [82]. On the other hand, using a dose of 0.83 mg/kg, anxiety symptoms (EPM and LD) could be observed until 7 days after LPS administration [79]. In 2 different studies from the same group, it was possible to observe depressive symptoms at 28 days after 0.83 mg/kg LPS administration in one [92] but not in the other [93] using the same mice strain.…”

Section: Discussionmentioning

confidence: 66%

“…However, most of the studies have only associated different alterations related to the kynenurine pathway [79,82,89,91,94,97,98,107,118,119,126,143,146], microglial activation [66,69,80,118,119,132,139,141], or astrocytic activation by the CXCL12/CXCR4 pathway [130]. The region most affected is always the hippocampus and/or the prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

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What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

et al. 2021

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Lower sepsis mortality rates imply that more patients are discharged from the hospital, but sepsis survivors often experience sequelae, such as functional disability, cognitive impairment, and psychiatric morbidity. Nevertheless, the mechanisms underlying these long-term disabilities are not fully understood. Considering the extensive use of animal models in the study of the pathogenesis of neuropsychiatric disorders, it seems adopting this approach to improve our knowledge of postseptic psychiatric symptoms is a logical approach. With the purpose of gathering and summarizing the main findings of studies using animal models of sepsis-induced psychiatric symptoms, we performed a systematic review of the literature on this topic. Thus, 140 references were reviewed, and most of the published studies suggested a time-dependent recovery from behavior alterations, despite the fact that some molecular alterations persist in the brain. This review reveals that animal models can be used to understand the mechanisms that underlie anxiety and depression in animals recovering from sepsis.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

et al. 2021

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“…According to a study conducted by Bhatt et al , 2017, 5-HT 3 RA are able to reduce the inflammation and anxiety induced by lipopolysaccharide in mice. In addition to the anxiolytic effect, 5-HT 3 RA are able to produce an anti-oxidant effect as well via enhancing the levels of anti-oxidant enzymes such as catalase and superoxide dismutase [ 125 ]. Tropisetron found to inhibit lipopolysaccharide induced increased levels of TNF-alpha and IL-1B in monocytes and serotonin induced prostaglandin E2 release from synovial cells [ 27 ].…”

Section: Immunomodulationmentioning

confidence: 99%

5-HT3 Receptor Antagonism: A Potential Therapeutic Approach for the Treatment of Depression and other Disorders

Bhatt

Devadoss

Manjula

et al. 2021

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Background: Depression or Major depressive disorder (MDD) is prolonged condition of sadness. MDD is the most common mental disorder that affects more than 264 million people worldwide. According to monoamine hypothesis, serotonin (5-hydroxy tryptamine, 5-HT), dopamine (DA) and norepinephrine (NE) are the major neurotransmitters (NTs) involved in depression. Method: The methodology adopted for writing this review article is essentially based on the secondary literature search through systematic literature review. This review mainly focussed on the role of 5-HT3 receptor antagonists (5-HT3RA) in depression and comorbid disorder like anxiety. Results: Out of three major NTs mentioned above, serotonin has predominant role in the pathophysiology of depression. The serotonin type-3 receptors (5-HT3R) are well renowned to be expressed in the central nervous system (CNS) in regions which have significance in the vomiting reflex, perception of pain, the reward system, cognition, depression and anxiety control. The 5-HT3R is only receptor of serotonergic family that belongs to ligand gated ion channel. The 5-HT3RA inhibit the binding of serotonin to post synaptic 5-HT3R and increase its availability to other receptors like 5-HT1A, 1B and 1D as well as 5-HT2 receptors and produces anti-depressant-like effect. The 5-HT3RA also have important role in mood and stress disorders. Some of the studies have shown the effectiveness of these agents in stress disorder. Conclusion: The present article focused on the role of 5-HT3R and their antagonists in the treatment of depression and anxiety. Further studies are warranted to prove their efficacy with respect to other standard anti-depressants.

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“…The administration of the compound together with fluoxetine reduced anxiety symptoms induced by LPS in all tested models. Increase in serotonin levels was also observed, which could intensify such symptoms; however, it was possibly prevented by the action of the 5-HT 3 antagonist [ 105 ]. 5-HT 3 receptor antagonists have an advantage over benzodiazepines for the treatment of anxiety, as they do not present sedative or hypnotic activity and there is no evidence of dependence.…”

Section: 5-ht 3 Receptorsmentioning

confidence: 99%

Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence

et al. 2021

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Serotonin (5-HT) receptors are found throughout central and peripheral nervous systems, mainly in brain regions involved in the neurobiology of anxiety and depression. 5-HT receptors are currently promising targets for discovering new drugs for treating disorders ranging from migraine to neuropsychiatric upsets, such as anxiety and depression. It is well described in the current literature that the brain expresses seven types of 5-HT receptors comprising eighteen distinct subtypes. In this article, we comprehensively reviewed 5-HT1-7 receptors. Of the eighteen 5-HT receptors known today, thirteen are G protein-coupled receptors (GPCRs) and represent targets for approximately 40% of drugs used in humans. Signaling pathways related to these receptors play a crucial role in neurodevelopment and can be modulated to develop effective therapies to treat anxiety and depression. This review presents the experimental evidence of the modulation of the “serotonergic receptosome” in the treatment of anxiety and depression, as well as demonstrating state-of-the-art research related to phytochemicals and these disorders. In addition, detailed aspects of the pharmacological mechanism of action of all currently known 5-HT receptor families were reviewed. From this review, it will be possible to direct the rational design of drugs towards new therapies that involve signaling via 5-HT receptors.

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Neuropharmacological evaluation of a novel 5-HT₃ receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice

Cited by 16 publications

References 27 publications

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

5-HT3 Receptor Antagonism: A Potential Therapeutic Approach for the Treatment of Depression and other Disorders

Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence

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Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice

Cited by 16 publications

References 27 publications

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

5-HT3 Receptor Antagonism: A Potential Therapeutic Approach for the Treatment of Depression and other Disorders

Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence

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Resources

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Neuropharmacological evaluation of a novel 5-HT₃ receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice