Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine ("ecstasy") users: Relationship to cognitive performance

Una D McCann, Zsolt Szabo, Melin Vranesic, Michael Palermo, William B Mathews, Hayden T. Ravert, Robert F Dannals, George Ricaurte

Research output: Contribution to journalArticle

Abstract

Background: (±)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance. Materials and methods: Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [11C]WIN 35,428 and [11C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing. Results: MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship. Conclusions: Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalPsychopharmacology
Volume200
Issue number3
DOIs
StatePublished - Oct 2008

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N-Methyl-3,4-methylenedioxyamphetamine
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Electrons
Brain
Serotonin
Prefrontal Cortex
Corpus Striatum
Parietal Lobe
Dopaminergic Neurons
Neurotoxins
Street Drugs
Positron-Emission Tomography
Rodentia

Keywords

  • Amphetamines
  • Dopamine
  • Memory
  • Neurotoxicity
  • Pharmacokinetics
  • Positron emission tomography
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine ({"}ecstasy{"}) users: Relationship to cognitive performance",
abstract = "Background: (±)3,4-Methylenedioxymethamphetamine (MDMA, {"}ecstasy{"}) is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance. Materials and methods: Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [11C]WIN 35,428 and [11C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing. Results: MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship. Conclusions: Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density.",
keywords = "Amphetamines, Dopamine, Memory, Neurotoxicity, Pharmacokinetics, Positron emission tomography, Serotonin",
author = "McCann, {Una D} and Zsolt Szabo and Melin Vranesic and Michael Palermo and Mathews, {William B} and Ravert, {Hayden T.} and Dannals, {Robert F} and George Ricaurte",
year = "2008",
month = "10",
doi = "10.1007/s00213-008-1218-4",
language = "English (US)",
volume = "200",
pages = "439--450",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "3",

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TY - JOUR

T1 - Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine ("ecstasy") users

T2 - Relationship to cognitive performance

AU - McCann, Una D

AU - Szabo, Zsolt

AU - Vranesic, Melin

AU - Palermo, Michael

AU - Mathews, William B

AU - Ravert, Hayden T.

AU - Dannals, Robert F

AU - Ricaurte, George

PY - 2008/10

Y1 - 2008/10

N2 - Background: (±)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance. Materials and methods: Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [11C]WIN 35,428 and [11C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing. Results: MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship. Conclusions: Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density.

AB - Background: (±)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance. Materials and methods: Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [11C]WIN 35,428 and [11C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing. Results: MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship. Conclusions: Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density.

KW - Amphetamines

KW - Dopamine

KW - Memory

KW - Neurotoxicity

KW - Pharmacokinetics

KW - Positron emission tomography

KW - Serotonin

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U2 - 10.1007/s00213-008-1218-4

DO - 10.1007/s00213-008-1218-4

M3 - Article

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AN - SCOPUS:51849123181

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