Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice
Data(s) |
23/11/2009
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Resumo |
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin/dopamine interactions in the behavioral effects of MDMA remains unclear. We previously showed that MDMA-induced locomotion, serotonin and dopamine release are 5-HT(2B) receptor-dependent. The aim of the present study was to determine the contribution of serotonin and 5-HT(2B) receptors to the reinforcing properties of MDMA. We show here that 5-HT(2B) (-/-) mice do not exhibit behavioral sensitization or conditioned place preference following MDMA (10 mg/kg) injections. In addition, MDMA-induced reinstatement of conditioned place preference after extinction and locomotor sensitization development are each abolished by a 5-HT(2B) receptor antagonist (RS127445) in wild type mice. Accordingly, MDMA-induced dopamine D1 receptor-dependent phosphorylation of extracellular regulated kinase in nucleus accumbens is abolished in mice lacking functional 5-HT(2B) receptors. Nevertheless, high doses (30 mg/kg) of MDMA induce dopamine-dependent but serotonin and 5-HT(2B) receptor-independent behavioral effects. These results underpin the importance of 5-HT(2B) receptors in the reinforcing properties of MDMA and illustrate the importance of dose-dependent effects of MDMA on serotonin/dopamine interactions. |
Formato |
application/pdf |
Identificador | |
Publicador |
Public Library of Science |
Relação |
http://eprints.qut.edu.au/73151/1/73151.pdf DOI:10.1371/journal.pone.0007952 Doly, Stephane, Bertran-Gonzalez, Jesus, Callebert, Jacques, Bruneau, Alexandra, Banas, Sophie Marie, Belmer, Arnauld, Boutourlinsky, Katia, Herve, Denis, Launay, Jean-Marie, & Maroteaux, Luc (2009) Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice. PLoS ONE, 4(11), e7952. |
Direitos |
Copyright 2009 Doly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Fonte |
School of Clinical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #110999 Neurosciences not elsewhere classified #5-HT2B #MDMA #Ecstasy |
Tipo |
Journal Article |