PMID- 2443644
OWN - NLM
STAT- MEDLINE
DCOM- 19871105
LR  - 20151119
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 242
IP  - 3
DP  - 1987 Sep
TI  - 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy 
      serotonin terminals in rat brain: quantification of neurodegeneration by 
      measurement of [3H]paroxetine-labeled serotonin uptake sites.
PG  - 911-6
AB  - This study examines the effects of repeated systemic administration (20 mg/kg 
      s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 
      3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their 
      metabolites and on the density of monoamine uptake sites in various regions of 
      rat brain. Marked reductions (30-60%) in the concentration of 
      5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, 
      striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of 
      MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed 
      in these brain regions. In addition, both MDMA and MDA caused comparable and 
      substantial reductions (50-75%) in the density of [3H]paroxetine-labeled 5-HT 
      uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA 
      caused any widespread or long-term changes in the content of the 
      catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 
      dihydroxyphenylacetic acid and homovanillic acid) or in the number of 
      [3H]mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions 
      examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic 
      effects with respect to both the functional and structural integrity of 
      serotonergic neurons in brain. Furthermore, our measurement of reductions in the 
      density of 5-HT uptake sites provides a means for quantification of the 
      neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.
FAU - Battaglia, G
AU  - Battaglia G
AD  - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland.
FAU - Yeh, S Y
AU  - Yeh SY
FAU - O'Hearn, E
AU  - O'Hearn E
FAU - Molliver, M E
AU  - Molliver ME
FAU - Kuhar, M J
AU  - Kuhar MJ
FAU - De Souza, E B
AU  - De Souza EB
LA  - eng
GR  - NS 15199/NS/NINDS NIH HHS/United States
GR  - NS 21011/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Amphetamines)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - 41VRH5220H (Paroxetine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/*toxicity
MH  - Amphetamines/*toxicity
MH  - Animals
MH  - Brain/*drug effects
MH  - Brain Chemistry/drug effects
MH  - Dopamine/metabolism
MH  - Hydroxyindoleacetic Acid/analysis
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Paroxetine
MH  - Piperidines/*metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, Serotonin/*drug effects
MH  - Serotonin/analysis/metabolism
MH  - Serotonin Antagonists/*metabolism
MH  - Tritium
EDAT- 1987/09/01 00:00
MHDA- 1987/09/01 00:01
CRDT- 1987/09/01 00:00
PHST- 1987/09/01 00:00 [pubmed]
PHST- 1987/09/01 00:01 [medline]
PHST- 1987/09/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1987 Sep;242(3):911-6.