PMID- 22353758
OWN - NLM
STAT- MEDLINE
DCOM- 20120814
LR  - 20221207
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 6
DP  - 2012 May
TI  - Sustained recreational use of ecstasy is associated with altered pre and 
      postsynaptic markers of serotonin transmission in neocortical areas: a PET study 
      with [(1)(1)C]DASB and [(1)(1)C]MDL 100907.
PG  - 1465-73
LID - 10.1038/npp.2011.332 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the 
      recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, 
      MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study 
      was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic 
      (5-HT(2A) receptor) markers of 5-HT transmission in recently abstinent chronic 
      MDMA users compared with matched healthy controls. We hypothesized that MDMA use 
      is associated with lower SERT density and concomitant upregulation of 5-HT(2A) 
      receptors. Positron emission tomography studies using the SERT ligand [(1)(1)C]DASB 
      and the 5-HT(2A) receptor ligand [(1)(1)C]MDL 100907 were evaluated in 13 current and 
      recently detoxified MDMA users and 13 matched healthy controls. MDMA users 
      reported a mean duration of ecstasy use of 8 years, regular exposure, and at 
      least 2 weeks of abstinence before the scans. SERT and 5-HT(2A) receptor 
      availability (binding potential, BP(ND)) were analyzed with a two-tissue 
      compartment model with arterial input function. Current recreational MDMA use was 
      significantly associated with lower SERT BP(ND) and higher 5-HT(2A) receptor 
      BP(ND) in cortical, but not subcortical regions. Decreased SERT BP(ND) was 
      regionally associated with upregulated 5-HT(2A) receptor BP(ND). In light of the 
      animal literature, the most parsimonious interpretation is that repeated exposure 
      to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron 
      terminals innervating the cortex. Alterations in mood, cognition, and impulse 
      control associated with these changes might contribute to sustain MDMA use. The 
      reversibility of these changes upon abstinence remains to be firmly established.
FAU - Urban, Nina Bl
AU  - Urban NB
AD  - Department of Psychiatry, Columbia University, New York State Psychiatric 
      Institute, New York, NY 10032, USA. nu2118@columbia.edu
FAU - Girgis, Ragy R
AU  - Girgis RR
FAU - Talbot, Peter S
AU  - Talbot PS
FAU - Kegeles, Lawrence S
AU  - Kegeles LS
FAU - Xu, X
AU  - Xu X
FAU - Frankle, W Gordon
AU  - Frankle WG
FAU - Hart, Carl L
AU  - Hart CL
FAU - Slifstein, Mark
AU  - Slifstein M
FAU - Abi-Dargham, Anissa
AU  - Abi-Dargham A
FAU - Laruelle, Marc
AU  - Laruelle M
LA  - eng
GR  - R01 DA015806/DA/NIDA NIH HHS/United States
GR  - R01 DA015806-02/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120222
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Benzylamines)
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Fluorobenzenes)
RN  - 0 (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine)
RN  - 0 (Piperidines)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Serotonin 5-HT2 Receptor Antagonists)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - EW71EE171J (volinanserin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adult
MH  - Amphetamine-Related Disorders/diagnostic imaging/*pathology
MH  - Benzylamines/*pharmacokinetics
MH  - Brain Mapping
MH  - Carbon Radioisotopes/pharmacokinetics
MH  - Female
MH  - Fluorobenzenes/*pharmacokinetics
MH  - Humans
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neocortex/*diagnostic imaging/drug effects
MH  - Piperidines/*pharmacokinetics
MH  - Positron-Emission Tomography
MH  - Protein Binding/drug effects
MH  - Receptor, Serotonin, 5-HT2A/metabolism
MH  - Serotonin 5-HT2 Receptor Antagonists/*pharmacokinetics
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Selective Serotonin Reuptake Inhibitors/*pharmacokinetics
MH  - Young Adult
PMC - PMC3327851
EDAT- 2012/02/23 06:00
MHDA- 2012/08/15 06:00
PMCR- 2013/05/01
CRDT- 2012/02/23 06:00
PHST- 2012/02/23 06:00 [entrez]
PHST- 2012/02/23 06:00 [pubmed]
PHST- 2012/08/15 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - npp2011332 [pii]
AID - 10.1038/npp.2011.332 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 May;37(6):1465-73. doi: 10.1038/npp.2011.332. Epub 
      2012 Feb 22.