Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice | Zendy

Stéphane Doly | Zendy; Jesus BertranGonzalez | Zendy; Jacques Callebert | Zendy; Alexandra Bruneau | Zendy; Sophie M. Banas | Zendy; Arnauld Belmer | Zendy; Katia Boutourlinsky | Zendy; Denis Hervé | Zendy; JeanMarie Launay | Zendy; Luc Maroteaux | Zendy

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Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice

Author(s) -

Stéphane Doly,

Jesus BertranGonzalez,

Jacques Callebert,

Alexandra Bruneau,

Sophie M. Banas,

Arnauld Belmer,

Katia Boutourlinsky,

Denis Hervé,

JeanMarie Launay,

Luc Maroteaux

Publication year - 2009

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0007952

Subject(s) - mdma , serotonin , dopamine , pharmacology , 5 ht receptor , nucleus accumbens , amphetamine , conditioned place preference , dopamine receptor d1 , dopamine receptor d2 , ecstasy , chemistry , endogenous agonist , receptor , biology , neuroscience , psychology , biochemistry , psychiatry

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.

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