Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro. - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Journal of Neuroscience Année : 2008

Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro.

Résumé

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.
Fichier principal
Vignette du fichier
2933.pdf (712.28 Ko) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

inserm-00484533 , version 1 (21-05-2010)

Identifiants

Citer

Stéphane Doly, Emmanuel Valjent, Vincent Setola, Jacques Callebert, Denis Hervé, et al.. Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro.. Journal of Neuroscience, 2008, 28 (11), pp.2933-40. ⟨10.1523/JNEUROSCI.5723-07.2008⟩. ⟨inserm-00484533⟩
309 Consultations
299 Téléchargements

Altmetric

Partager

More