Positron Emission Tomographic Studies of Brain Dopamine and Serotonin Transporters in Abstinent (±) 3,4-Methylenedioxymethamphetamine (“Ecstasy”) Users: Relationship to Cognitive Performance
Identifieur interne : 000323 ( Main/Exploration ); précédent : 000322; suivant : 000324Positron Emission Tomographic Studies of Brain Dopamine and Serotonin Transporters in Abstinent (±) 3,4-Methylenedioxymethamphetamine (“Ecstasy”) Users: Relationship to Cognitive Performance
Auteurs : Una D. Mccann [États-Unis] ; Zsolt Szabo [États-Unis] ; Melin Vranesic [États-Unis] ; Michael Palermo [États-Unis] ; William B. Mathews [États-Unis] ; Hayden T. Ravert [États-Unis] ; Robert F. Dannals [États-Unis] ; George A. Ricaurte [États-Unis]Source :
- Psychopharmacology [ 0033-3158 ] ; 2008.
Abstract
(±)3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA damages 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. We sought to determine whether MDMA users who take closely spaced sequential doses develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance.
Sixteen abstinent MDMA users with a history of sequential MDMA use (two or more doses over a 3-12 hour period) and sixteen age and gender- 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.
MDMA users had reduced 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.
Sequential MDMA use 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.
Url:
DOI: 10.1007/s00213-008-1218-4
PubMed: 18661256
PubMed Central: 2789420
Affiliations:
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Mccann</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Szabo, Zsolt" sort="Szabo, Zsolt" uniqKey="Szabo Z" first="Zsolt" last="Szabo">Zsolt Szabo</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Vranesic, Melin" sort="Vranesic, Melin" uniqKey="Vranesic M" first="Melin" last="Vranesic">Melin Vranesic</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Palermo, Michael" sort="Palermo, Michael" uniqKey="Palermo M" first="Michael" last="Palermo">Michael Palermo</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mathews, William B" sort="Mathews, William B" uniqKey="Mathews W" first="William B." last="Mathews">William B. Mathews</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ravert, Hayden T" sort="Ravert, Hayden T" uniqKey="Ravert H" first="Hayden T." last="Ravert">Hayden T. Ravert</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Dannals, Robert F" sort="Dannals, Robert F" uniqKey="Dannals R" first="Robert F." last="Dannals">Robert F. Dannals</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ricaurte, George A" sort="Ricaurte, George A" uniqKey="Ricaurte G" first="George A." last="Ricaurte">George A. Ricaurte</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">Psychopharmacology</title><idno type="ISSN">0033-3158</idno><idno type="eISSN">1432-2072</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Rationale</title><p id="P1">(±)3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA damages 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. We sought to determine whether MDMA users who take closely spaced sequential doses develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance.</p></sec><sec sec-type="methods" id="S2"><title>Methods</title><p id="P2">Sixteen abstinent MDMA users with a history of sequential MDMA use (two or more doses over a 3-12 hour period) and sixteen age and gender- matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [<sup>11</sup>C]WIN 35,428 and [<sup>11</sup>C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing.</p></sec><sec id="S3"><title>Results</title><p id="P3">MDMA users had reduced 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.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Sequential MDMA use 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.</p></sec></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Mccann, Una D" sort="Mccann, Una D" uniqKey="Mccann U" first="Una D." last="Mccann">Una D. Mccann</name></region><name sortKey="Dannals, Robert F" sort="Dannals, Robert F" uniqKey="Dannals R" first="Robert F." last="Dannals">Robert F. Dannals</name><name sortKey="Mathews, William B" sort="Mathews, William B" uniqKey="Mathews W" first="William B." last="Mathews">William B. Mathews</name><name sortKey="Palermo, Michael" sort="Palermo, Michael" uniqKey="Palermo M" first="Michael" last="Palermo">Michael Palermo</name><name sortKey="Ravert, Hayden T" sort="Ravert, Hayden T" uniqKey="Ravert H" first="Hayden T." last="Ravert">Hayden T. Ravert</name><name sortKey="Ricaurte, George A" sort="Ricaurte, George A" uniqKey="Ricaurte G" first="George A." last="Ricaurte">George A. Ricaurte</name><name sortKey="Szabo, Zsolt" sort="Szabo, Zsolt" uniqKey="Szabo Z" first="Zsolt" last="Szabo">Zsolt Szabo</name><name sortKey="Vranesic, Melin" sort="Vranesic, Melin" uniqKey="Vranesic M" first="Melin" last="Vranesic">Melin Vranesic</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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