6z, a novel 5HT3 receptor antagonist reverses depression-like behavior in streptozotocin-induced diabetic mice by normalizing serotonin deficiency and HPA-axis hyperactivity.

Abstract

Event Abstract Back to Event 6z, a novel 5HT3 receptor antagonist reverses depression-like behavior in streptozotocin-induced diabetic mice by normalizing serotonin deficiency and HPA-axis hyperactivity. Deepali Gupta1* and Radhakrishnan Mahesh1 1 Birla Institute of Technology and Science, Department of Pharmacy, India Individuals with diabetes are three times more likely to have depression than without it. The impairment of brain serotonin activity and hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity has been linked with the pathogenesis of depression in diabetes, while antagonism of 5HT3 receptors (5HT3Rs) has been shown to facilitate serotonin neurotransmission and normalize HPA-axis hyperactivity in animal models of depression. In addition, 5HT3Rs have been implicated in regulation of glucose homeostasis and energy metabolism. We earlier reported that 6z (N-(Benzo [d]thiazol-2-yl)-3-methoxyquinoxalin-2-carboxamide), a novel 5HT3R antagonist posses potential antidepressant activity in preclinical models of depression. In extension to that, the present study was aimed at investigating the antidepressant-like effects of 6z, in depression associated with diabetes. Mice with 8 weeks of streptozotocin (STZ)-induced diabetes were given vehicle/ 6z (1 and 2 mg/kg, i.p.)/ fluoxetine (10 mg/kg, i.p.) for 21 days and then subjected to neurobehavioral models including forced swim test (FST), tail suspension test (TST), hole board test (HBT) and light-dark test (LDT). 24 hrs after the last behavioral assay mice were decapitated, and blood and brains were collected for biochemical analysis. Results showed that STZ-induced diabetic mice exhibited a significant despair behavior (increased duration of immobility) in FST and TST, and reduced exploratory behavior indicated by reduced head dipping activity and exposure to bright chamber in HBT and LDT respectively. This was accompanied by reduced serotonin levels in discrete brain regions and elevated plasma corticosterone levels (a marker of HPA-axis hyperactivity). 6z (1 and 2 mg/kg), similar to fluoxetine reversed diabetes-induced behavioral and biochemical perturbations. It suggests that 6z was able to reverse diabetes-induced depression-like behavior mice and its antidepressant effect was associated with normalization of serotonin deficits and HPA-axis hyperactivity. Keywords: Depression, in vivo, diabetes, hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity, neurobehavioural test Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: O02: Postgraduate Travel Awardees Oral Session 2 Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Gupta D and Mahesh R (2016). 6z, a novel 5HT3 receptor antagonist reverses depression-like behavior in streptozotocin-induced diabetic mice by normalizing serotonin deficiency and HPA-axis hyperactivity.. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00086 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Ms. Deepali Gupta, Birla Institute of Technology and Science, Department of Pharmacy, Pilani, Rajasthan, India, deepaligupta2010@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Deepali Gupta Radhakrishnan Mahesh Google Deepali Gupta Radhakrishnan Mahesh Google Scholar Deepali Gupta Radhakrishnan Mahesh PubMed Deepali Gupta Radhakrishnan Mahesh Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.