PMID- 18337424
OWN - NLM
STAT- MEDLINE
DCOM- 20080408
LR  - 20220408
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 11
DP  - 2008 Mar 12
TI  - Serotonin 5-HT2B receptors are required for 
      3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in 
      vivo and in vitro.
PG  - 2933-40
LID - 10.1523/JNEUROSCI.5723-07.2008 [doi]
AB  - 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.
FAU - Doly, Stephane
AU  - Doly S
AD  - Inserm, U839 and Universite Pierre et Marie Curie-Paris 6, Institut du Fer a 
      Moulin, Unite Mixte de Recherche-S0839, Paris 75005, France.
FAU - Valjent, Emmanuel
AU  - Valjent E
FAU - Setola, Vincent
AU  - Setola V
FAU - Callebert, Jacques
AU  - Callebert J
FAU - Herve, Denis
AU  - Herve D
FAU - Launay, Jean-Marie
AU  - Launay JM
FAU - Maroteaux, Luc
AU  - Maroteaux L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Receptor, Serotonin, 5-HT2B)
RN  - 0 (Serotonin 5-HT2 Receptor Antagonists)
RN  - 0 (Serotonin Antagonists)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Female
MH  - Hyperkinesis/chemically induced/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology/toxicity
MH  - Protein Binding/drug effects/physiology
MH  - Receptor, Serotonin, 5-HT2B/*metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin 5-HT2 Receptor Antagonists
MH  - Serotonin Antagonists/pharmacology
PMC - PMC6670669
EDAT- 2008/03/14 09:00
MHDA- 2008/04/09 09:00
PMCR- 2008/09/12
CRDT- 2008/03/14 09:00
PHST- 2008/03/14 09:00 [pubmed]
PHST- 2008/04/09 09:00 [medline]
PHST- 2008/03/14 09:00 [entrez]
PHST- 2008/09/12 00:00 [pmc-release]
AID - 28/11/2933 [pii]
AID - 3323949 [pii]
AID - 10.1523/JNEUROSCI.5723-07.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Mar 12;28(11):2933-40. doi: 10.1523/JNEUROSCI.5723-07.2008.