PMID- 22079770
OWN - NLM
STAT- MEDLINE
DCOM- 20120503
LR  - 20211021
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 674
IP  - 2-3
DP  - 2012 Jan 15
TI  - Effects of MDMA and related analogs on plasma 5-HT: relevance to 5-HT 
      transporters in blood and brain.
PG  - 337-44
LID - 10.1016/j.ejphar.2011.10.033 [doi]
AB  - (+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that evokes 
      transporter-mediated release of serotonin (5-HT) in the brain. 5-HT transporter 
      (SERT) proteins are also expressed in non-neural tissues (e.g., blood), and 
      evidence suggests that MDMA targets platelet SERT to increase plasma 5-HT. Here 
      we tested two hypotheses related to the effects of MDMA on circulating 5-HT. 
      First, to determine if MDMA metabolites might contribute to actions of the drug 
      in vivo, we used in vitro microdialysis in rat blood specimens to examine the 
      effects of MDMA and its metabolites on plasma 5-HT. Second, to determine whether 
      effects of MDMA on plasma 5-HT might be used as an index of central SERT 
      activity, we carried out in vivo microdialysis in blood and brain after 
      intravenous MDMA administration. The in vitro results show that test drugs evoke 
      dose-related increases in plasma 5-HT ranging from two- to sevenfold above 
      baseline, with MDMA and its metabolite, (+/-)-3,4-methylenedioxyamphetamine (MDA), 
      producing the largest effects. The ability of MDMA and related analogs to elevate 
      plasma 5-HT is correlated with their potency as SERT substrates in rat brain 
      synaptosomes. The in vivo results reveal that MDMA causes concurrent increases in 
      extracellular 5-HT in blood and brain, but there are substantial individual 
      differences in responsiveness to the drug. Collectively, our findings indicate 
      that MDMA and its metabolites increase plasma 5-HT by a SERT-dependent mechanism, 
      and suggest the possibility that measures of evoked 5-HT release in blood may 
      reflect central SERT activity.
CI  - Published by Elsevier B.V.
FAU - Yubero-Lahoz, Samanta
AU  - Yubero-Lahoz S
AD  - Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences 
      Research Program, IMIM-Hospital del Mar Research Institute, Barcelona, Spain.
FAU - Ayestas, Mario A Jr
AU  - Ayestas MA Jr
FAU - Blough, Bruce E
AU  - Blough BE
FAU - Partilla, John S
AU  - Partilla JS
FAU - Rothman, Richard B
AU  - Rothman RB
FAU - de la Torre, Rafael
AU  - de la Torre R
FAU - Baumann, Michael H
AU  - Baumann MH
LA  - eng
GR  - R01 DA017987/DA/NIDA NIH HHS/United States
GR  - Z01 DA000523-01/Intramural NIH HHS/United States
GR  - Z99 DA999999/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111103
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/*metabolism
MH  - Male
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*analogs & 
      derivatives/metabolism/*pharmacology
MH  - Protein Transport/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*blood/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/*blood/*metabolism
PMC - PMC3253888
MID - NIHMS335997
EDAT- 2011/11/15 06:00
MHDA- 2012/05/04 06:00
PMCR- 2013/01/15
CRDT- 2011/11/15 06:00
PHST- 2011/07/01 00:00 [received]
PHST- 2011/10/13 00:00 [revised]
PHST- 2011/10/27 00:00 [accepted]
PHST- 2011/11/15 06:00 [entrez]
PHST- 2011/11/15 06:00 [pubmed]
PHST- 2012/05/04 06:00 [medline]
PHST- 2013/01/15 00:00 [pmc-release]
AID - S0014-2999(11)01401-4 [pii]
AID - 10.1016/j.ejphar.2011.10.033 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2012 Jan 15;674(2-3):337-44. doi: 10.1016/j.ejphar.2011.10.033. 
      Epub 2011 Nov 3.