PMID- 15266556
OWN - NLM
STAT- MEDLINE
DCOM- 20041110
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 53
IP  - 4
DP  - 2004 Sep 15
TI  - 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain 
      tissue serotonin but not serotonin transporter protein and glial fibrillary 
      acidic protein.
PG  - 240-8
AB  - Previous experiments conducted in this laboratory showed that administration of 
      high-dose D-fenfluramine (D-FEN) and p-chloroamphetamine (PCA) decreased 5-HT 
      transporter (SERT) binding and tissue 5-HT by 30-60% in caudate and whole brain 
      tissue 2 days and 2 weeks after drug administration. However, protein expression 
      as determined by Western blot analysis did not change in either tissue or time 
      point, except for a 30% decrease in the caudate 2 days after PCA administration. 
      In the present study, we studied the effect of MDMA and 5,7-dihydroxytryptamine 
      (5,7-DHT) on tissue 5-HT levels and the protein expression level of SERT and 
      glial fibrillary acidic protein (GFAP), a validated neurotoxicity marker. 
      HYPOTHESIS: MDMA administration decreases SERT expression. METHODS: Two weeks 
      after MDMA administration (7.5 mg/kg i.p., q 2 h x 3 doses) or 2 weeks after 
      i.c.v. administration of 5,7,-DHT (150 microg/rat), male Sprague-Dawley rats were 
      sacrificed and the caudate, cortex, and hippocampal tissue collected. Western 
      blots for SERT and GFAP were generated using published methods. Tissue 5-HT 
      levels were determined by HPLC coupled to electrochemical detection. RESULTS: 
      MDMA treatment decreased tissue 5-HT in cortex, hippocampus, and caudate by about 
      50%. However, MDMA treatment had no significant effect on expression level of 
      SERT and GFAP in any brain region. In contrast, 5,7-DHT reduced tissue 5-HT by 
      more than 90%, decreased SERT protein expression by 20-35%, and increased GFAP by 
      30-39%. CONCLUSION: These data suggest the MDMA treatment regimen used here does 
      not cause degeneration of 5-HT nerve terminals. Viewed collectively with our 
      previous results and other published data, these data indicate that MDMA-induced 
      persistent 5-HT depletion may occur in the absence of axotomy.
FAU - Wang, Xiaoying
AU  - Wang X
AD  - Clinical Psychopharmacology Section, Intramural Research Program, National 
      Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 
      21224, USA.
FAU - Baumann, Michael H
AU  - Baumann MH
FAU - Xu, Heng
AU  - Xu H
FAU - Rothman, Richard B
AU  - Rothman RB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Carrier Proteins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 31363-74-3 (5,7-Dihydroxytryptamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - 5,7-Dihydroxytryptamine/pharmacology
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Brain/*drug effects/metabolism
MH  - Brain Chemistry/*drug effects/physiology
MH  - Carrier Proteins/*drug effects/metabolism
MH  - Down-Regulation/drug effects/physiology
MH  - Glial Fibrillary Acidic Protein/*drug effects/metabolism
MH  - Homovanillic Acid/metabolism
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - Membrane Glycoproteins/*drug effects/metabolism
MH  - *Membrane Transport Proteins
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Nerve Tissue Proteins/*drug effects/metabolism
MH  - Neurons/drug effects/metabolism
MH  - Neurotoxins/pharmacology
MH  - Norepinephrine/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Up-Regulation/drug effects/physiology
EDAT- 2004/07/22 05:00
MHDA- 2004/11/13 09:00
CRDT- 2004/07/22 05:00
PHST- 2004/07/22 05:00 [pubmed]
PHST- 2004/11/13 09:00 [medline]
PHST- 2004/07/22 05:00 [entrez]
AID - 10.1002/syn.20058 [doi]
PST - ppublish
SO  - Synapse. 2004 Sep 15;53(4):240-8. doi: 10.1002/syn.20058.