Modulation of P2X7 receptor function alters depressive behavior in rodent models of depression

Abstract

Event Abstract Back to Event Modulation of P2X7 receptor function alters depressive behavior in rodent models of depression Rómeó Andó1*, Flóra Gölöncsér1 and Beáta Sperlágh1 1 Institute of Experimental Medicine Hungarian Academy of Sciences, Laboratory of Molecular Pharmacology, Hungary Introduction: The purinergic P2X7 receptors (P2X7R), play an important role in the modulation of the neurotransmitter release and in the posttranslational processing of the proinflammatory cytokine, IL-1beta ï€ after bacterial endotoxin challenge. Recent gene polymorphism studies indicate significant association of a gain of function mutation of the gene encoding P2X7R with both major depressive disorder and bipolar disorder. We investigated the possible modulatory effects of P2X7 receptor on depressive-like behavior under basal conditions and after lipopolysaccharide (LPS) treatment in rodent models of depression. Methods: Behavioral tests of depression, namely, forced swim test (FST) and automated tail suspension test (TST) were carried out in wild-type and P2X7 receptor knockout B6/6J mice and the time of immobility was measured. The effects of intraperitoneal lipopolysaccharide (LPS) and the effects of acute and chronic treatments with the P2X7R antagonist Brilliant Blue G (BBG) were investigated. Results: P2X7R knockout mice displayed antidepressant phenotype in both behavioral tests, as indicated by the significant decrease in the time of immobility. Lipopolysaccharide (1 mg/kg, i.p.) treatment increased immobility in both behavioural models in the wild-type mice. However, in P2X7 knockout animals, the effects of LPS were significantly attenuated in the TST and reversed in the FST. Acute treatment with BBG was without effect in wild-type mice but chronic treatment for 1 week dose-dependently decreased immobility (25-50 mg/kg i.p.). Acute BBG administration also attenuated the LPS-induced depressive-like behavior in the TST. Conclusions: The antidepressant phenotype of P2X7R KO mice and the attenuation of LPS-induced depressive behavior by the inhibition of P2X7R is an indication for the role of P2X7 receptors in the pathophysiology of depressive disorders, and suggest that P2X7R antagonists may represent a novel target in the therapeutics of depression. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cognition and behavior Citation: Andó R, Gölöncsér F and Sperlágh B (2010). Modulation of P2X7 receptor function alters depressive behavior in rodent models of depression. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00141 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: 29 Apr 2010; Published Online: 29 Apr 2010. * Correspondence: Rómeó Andó, Institute of Experimental Medicine Hungarian Academy of Sciences, Laboratory of Molecular Pharmacology, Budapest, Hungary, ando@koki.hu 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 Rómeó Andó Flóra Gölöncsér Beáta Sperlágh Google Rómeó Andó Flóra Gölöncsér Beáta Sperlágh Google Scholar Rómeó Andó Flóra Gölöncsér Beáta Sperlágh PubMed Rómeó Andó Flóra Gölöncsér Beáta Sperlágh 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.