PMID- 16452989
OWN - NLM
STAT- MEDLINE
DCOM- 20070105
LR  - 20150311
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 31
IP  - 12
DP  - 2006 Dec
TI  - Loss of serotonin transporter protein after MDMA and other ring-substituted 
      amphetamines.
PG  - 2639-51
AB  - We studied in vivo expression of the serotonin transporter (SERT) protein after 
      3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or 
      fenfluramine (FEN) treatments, and compared the effects of substituted 
      amphetamines to those of 5,7-dihydroxytryptamine (5,7-DHT), an established 
      serotonin (5-HT) neurotoxin. All drug treatments produced lasting reductions in 
      5-HT, 5-HIAA, and [(3)H]paroxetine binding, but no significant change in the 
      density of a 70 kDa band initially thought to correspond to the SERT protein. 
      Additional Western blot studies, however, showed that the 70 kDa band did not 
      correspond to the SERT protein, and that a diffuse band at 63-68 kDa, one that 
      had the anticipated regional brain distribution of SERT protein 
      (midbrain>striatum>neocortex>cerebellum), was reduced after 5,7-DHT and was 
      absent in SERT-null animals, was decreased after MDMA, PCA, or FEN treatments. In 
      situ immunocytochemical (ICC) studies with the same two SERT antisera used in 
      Western blot studies showed loss of SERT-immunoreactive (IR) axons after 5,7-DHT 
      and MDMA treatments. In the same animals, tryptophan hydroxylase (TPH)-IR axon 
      density was comparably reduced, indicating that serotonergic deficits after 
      substituted amphetamines differ from those in SERT-null animals, which have 
      normal TPH levels but, in the absence of SERT, develop apparent neuroadaptive 
      changes in 5-HT metabolism. Together, these results suggest that lasting 
      serotonergic deficits after MDMA and related drugs are unlikely to represent 
      neuroadaptive metabolic responses to changes in SERT trafficking, and favor the 
      view that substituted amphetamines have the potential to produce a distal axotomy 
      of brain 5-HT neurons.
FAU - Xie, Tao
AU  - Xie T
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 
      MD 21224, USA.
FAU - Tong, Liqiong
AU  - Tong L
FAU - McLane, Michael W
AU  - McLane MW
FAU - Hatzidimitriou, George
AU  - Hatzidimitriou G
FAU - Yuan, Jie
AU  - Yuan J
FAU - McCann, Una
AU  - McCann U
FAU - Ricaurte, George
AU  - Ricaurte G
LA  - eng
GR  - DA017964/DA/NIDA NIH HHS/United States
GR  - DA05707/DA/NIDA NIH HHS/United States
GR  - DA11226/DA/NIDA NIH HHS/United States
GR  - DA13790/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060125
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Neurotoxins)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 2DS058H2CF (Fenfluramine)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
EIN - Neuropsychopharmacology. 2008 Feb;33(3):712-3
MH  - 5,7-Dihydroxytryptamine/toxicity
MH  - Animals
MH  - Axons/drug effects/metabolism
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Down-Regulation/drug effects/physiology
MH  - Fenfluramine/toxicity
MH  - Immunohistochemistry
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects/chemistry
MH  - Neurotoxins/*adverse effects/chemistry
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*biosynthesis
MH  - Serotonin Agents/adverse effects/chemistry
MH  - Serotonin Plasma Membrane Transport Proteins/*drug effects/genetics/metabolism
MH  - Tryptophan Hydroxylase/metabolism
MH  - Wallerian Degeneration/*chemically induced/metabolism/physiopathology
MH  - p-Chloroamphetamine/toxicity
EDAT- 2006/02/03 09:00
MHDA- 2007/01/06 09:00
CRDT- 2006/02/03 09:00
PHST- 2006/02/03 09:00 [pubmed]
PHST- 2007/01/06 09:00 [medline]
PHST- 2006/02/03 09:00 [entrez]
AID - 1301031 [pii]
AID - 10.1038/sj.npp.1301031 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2006 Dec;31(12):2639-51. doi: 10.1038/sj.npp.1301031. 
      Epub 2006 Jan 25.