title: In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users.
abstract: BACKGROUND
  Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.
  
  
  OBJECTIVE
  To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin(2A) receptor binding.
  
  
  METHODS
  A positron emission tomography study of 24 young adult drug users and 21 nonusing control participants performed with carbon 11 ((11)C)-labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile (DASB) and fluorine 18 ((18)F)-labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14).
  
  
  METHODS
  Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls.
  
  
  METHODS
  In vivo cerebral SERT and serotonin(2A) receptor binding.
  
  
  RESULTS
  Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, -56%; pallidostriatum, -19%; and amygdala, -32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of lifetime MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin(2A) receptor binding in the serotonin(2A) receptor agonist users (both user groups) was also detected.
  
  
  CONCLUSIONS
  We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin(2A) receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin(2A) agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. d.erritzoe@imperial.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Holst
authors.forename: Maria
authors.initials: M
authors.lastname: Christoffersen
authors.forename: Sys S
authors.initials: SS
authors.lastname: Johansen
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rasmussen
authors.forename: Thomas
authors.initials: T
authors.lastname: Ramsøy
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005462:Fluorine Radioisotopes; D006213:Hallucinogens / Q000378:metabolism*; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D005462:Fluorine Radioisotopes; D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; C071983:altanserin; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine