BITS Faculty Publications
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Item Anxiolytic Effect of a Novel 5-HT3 Receptor Antagonist (4-Phenylpiperazin-1-yl)(Quinoxalin-2-yl) Methanone (4a) in a Battery of Behavioral Models for Anxiety in Mice(The Pharma Innovation, 2013) Mahesh, R.The serotonergic system of brain is well understood to play a crucial role in emotional processing in human and animals. 5-HT3 receptor, the ion channel type of receptor is involved in mood, anxiety, depression, learning and memory. Objective of the present work was to investigate the anxiolytic potential of a novel 5-HT3 receptor antagonist (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a) in mice. Different behavioral test paradigms for anxiety like elevated plus maze, open field test, light-dark model and hole board test were used for assessing the effect. Diazepam 2 mg/kg i.p. served as a reference standard. From the results it was found that 4a dose dependently at 2 and 4 mg/kg i.p. attenuated the behavioral alterations in the anxiety models in mice. The exact mechanism of 5- HT3 receptor antagonist for anxiolytic potential is still ill understood. Our further studies will deal with mechanisms at molecular levels for anxiolytic potential of 4aItem Antidepressant & anxiolytic activities of N-(pyridin-3-yl) quinoxalin-2-carboxamide: A novel serotonin type 3 receptor antagonist in behavioural animal models(IJMR, 2016) Mahesh, R.Alteration in the serotonin leads to the psychological illness, such as depression, anxiety, schizophrenia, eating disorders, obsessive-compulsive disorder, panic disorders and migraines. The objective of the current study was to investigate the antidepressant and anxiolytic activities of N-(pyridin-3-yl) quinoxalin-2-carboxamide (QCF-21), a novel 5-HT3 receptor antagonist in preclinical models of depression and anxiety.Item Anxiolytic-like effect of (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone (6g) in experimental mouse models of anxiety(Wolters Kluwer, 2013) Mahesh, R.The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT 3) receptor antagonist in experimental mouse models of anxiety.Item Anti-anxiety effect of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide (6k) using battery tests for anxiety in mice(Wolters Kluwer, 2014) Mahesh, R.To investigate the anti-anxiety activity of “6k”, a novel 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist in in mice.Item QCM-4, a 5-HT3 receptor antagonist ameliorates plasma HPA axis hyperactivity, leptin resistance and brain oxidative stress in depression and anxiety-like behavior in obese mice(Elsevier, 2015-01) Mahesh, R.Several preclinical studies have revealed antidepressant and anxiolytic-like effect of 5-HT3 receptor antagonists. In our earlier study, we have reported the antidepressive-like effect of 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) in obese mice subjected to chronic stress. The present study deals with the biochemical mechanisms associated with depression co-morbid with obesity. Mice were fed with high fat diet (HFD) for 14 weeks, further subjected for treatment with QCM-4 (1 and 2 mg/kg p.o.) and standard antidepressant escitalopram (ESC) (10 mg/kg p.o.) for 28 days. Behavioral assays for depression such as sucrose preference test (SPT), forced swim test (FST) and for anxiety such as light and dark test (LDT) and hole board test (HBT) were performed in obese mice. Biochemical assessments including plasma leptin and corticosterone concentration followed by brain oxidative stress parameters malonaldehyde (MDA) and reduced glutathione (GSH) were performed. Results confirmed that QCM-4 exhibits antidepressive effect by increasing the sucrose consumption in SPT, reducing immobility time in FST and anxiolytic effect by increasing transitions and time in light chamber in LDT, increasing head dip and crossing score in HBT. Furthermore, QCM-4 attenuated the hypothalamic–pituitary–adrenal (HPA) axis hyperactivity by reducing the plasma corticosterone, reversing altered plasma leptin, restoring the imbalance of brain MDA and GSH concentration. In conclusion, QCM-4 showed antidepressive and anxiolytic effect by reversing the behavioral alterations that were supported by biochemical estimations in obese mice.Item Depression-like and anxiety-like behavioural aftermaths of impact accelerated traumatic brain injury in rats: A model of comorbid depression and anxiety?(Elsevier, 2009-12) Mahesh, R.Depression and anxiety tend to be the most prevalent conditions among the multitude of neurobehavioural disorders which cause distress in the survivors of traumatic brain injury (TBI). The objective of the present investigation was to examine depression-like and anxiety-like behaviour of rats following diffuse TBI. Impact accelerated TBI was induced in anaesthetised rats by a modified weight drop method. TBI and sham-operated rats received either a chronic (14 days) regimen of escitalopram (5–20 mg/kg) or vehicle, following which they were subjected to a behavioural test battery. The results evince the depression-like behaviour of TBI rats in modified open field exploration, hyperemotionality, socio-sexual interaction and elevated plus-maze exploration paradigms. In addition, an anxiety-like behaviour was evident in social interaction and marble-burying tests. Chronic escitalopram (10 and 20 mg/kg) treatment significantly attenuated the TBI associated behavioural deficits. In conclusion, the aforesaid behavioural anomalies observed in TBI rats are analogous to comorbid anxiety and depression in humans. These findings substantiate the TBI rats as a candidate model of comorbid anxiety and depression.