Titre : | Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro |
Titre traduit : | (Les récepteurs 5-HT2B de la sérotonine sont requis dans l'hyperlocomotion induite par la 3,4-méthylènedioxyméthamphétamine et la libération de 5-HT in vivo et in vitro.) |
Auteurs : | DOLY S. ; VALJENT E. ; SETOLA V. ; CALLEBERT J. ; D. HERVE ; J. M. LAUNAY ; MAROTEAUX L. |
Type de document : | Périodique |
Année de publication : | 2008 |
Format : | 2933-2940 |
Note générale : |
Journal of Neuroscience, 2008, 28, (11), 2933-2940 |
Langues: | Français |
Discipline : | PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods) |
Mots-clés : |
Thésaurus mots-clés MODELE ANIMAL ; SEROTONINE ; RECEPTEUR ; COMPORTEMENT ; MDMA-ECSTASY ; TROUBLES DU COMPORTEMENT ; NEUROBIOLOGIE |
Résumé : |
ENGLISH : The "club drug" 3,4-methylenedioxymethamphetamine (MDMA; also known as ecstasy) binds preferentially to and reverses the activity of the serotonin transporter, causing release of serotonin [5-hydroxytryptamine (5-HT)] stores from nerve terminals. Subsequent activation of postsynaptic 5-HT receptors by released 5-HT has been shown to be critical for the unique psychostimulatory effects of MDMA. In contrast, the effects of direct activation of presynaptic and/or postsynaptic receptors by MDMA have received far less attention, despite the agonist actions of the drug itself at 5-HT(2) receptors, in particular the 5-HT(2B) receptor. Here we show that acute pharmacological inhibition or genetic ablation of the 5-HT(2B) receptor in mice completely abolishes MDMA-induced hyperlocomotion and 5-HT release in nucleus accumbens and ventral tegmental area. Furthermore, the 5-HT(2B) receptor dependence of MDMA-stimulated release of endogenous 5-HT from superfused midbrain synaptosomes suggests that 5-HT(2B) receptors act, unlike any other 5-HT receptor, presynaptically to affect MDMA-stimulated 5-HT release. Thus, our findings reveal a novel regulatory component in the actions of MDMA and represent the first demonstration that 5-HT(2B) receptors play an important role in the brain, i.e., modulation of 5-HT release. As such, 5-HT(2B) receptor antagonists may serve as promising therapeutic drugs for MDMA abuse. (Author' s abstract) |
Domaine : | Drogues illicites / Illicit drugs |
Affiliation : |
Inserm, U839 and Université Pierre et Marie Curie-Paris 6, Institut du Fer a Moulin, Unité Mixte de Recherche-S0839, Paris 75005 France. France. |
Numéro Toxibase : | 1302471 |
Centre Emetteur : | 13 OFDT |
Cote : | A03598 |
Exemplaires
Disponibilité |
---|
aucun exemplaire |
Accueil