Historique
Périodique
Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro
(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.)
Auteur(s) :
DOLY S. ;
VALJENT E. ;
SETOLA V. ;
CALLEBERT J. ;
HERVE, D. ;
LAUNAY, J. M. ;
MAROTEAUX L.
Année
2008
Page(s) :
2933-2940
Langue(s) :
Français
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Thésaurus mots-clés
MODELE ANIMAL
;
SEROTONINE
;
RECEPTEUR
;
COMPORTEMENT
;
MDMA-ECSTASY
;
TROUBLES DU COMPORTEMENT
;
NEUROBIOLOGIE
Note générale :
Journal of Neuroscience, 2008, 28, (11), 2933-2940
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)
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.
France. France.
Cote :
A03598