PMID- 16541247
OWN - NLM
STAT- MEDLINE
DCOM- 20070302
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 189
IP  - 4
DP  - 2007 Jan
TI  - 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of 
      past and present findings.
PG  - 407-24
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit 
      drug. In animals, high-dose administration of MDMA produces deficits in serotonin 
      (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as 
      neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of 
      ongoing debate. OBJECTIVE: The present paper reviews four specific issues related 
      to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on 
      monoamine neurons, (2) the use of "interspecies scaling" to adjust MDMA doses 
      across species, (3) the effects of MDMA on established markers of neuronal 
      damage, and (4) functional impairments associated with MDMA-induced 5-HT 
      depletions. RESULTS: MDMA is a substrate for monoamine transporters, and 
      stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA 
      produces neurochemical, endocrine, and behavioral actions in rats and humans at 
      equivalent doses (e.g., 1-2 mg/kg), suggesting that there is no reason to adjust 
      doses between these species. Typical doses of MDMA causing long-term 5-HT 
      depletions in rats (e.g., 10-20 mg/kg) do not reliably increase markers of 
      neurotoxic damage such as cell death, silver staining, or reactive gliosis. 
      MDMA-induced 5-HT depletions are accompanied by a number of functional 
      consequences including reductions in evoked 5-HT release and changes in hormone 
      secretion. Perhaps more importantly, administration of MDMA to rats induces 
      persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. 
      CONCLUSIONS: MDMA-induced 5-HT depletions are not necessarily synonymous with 
      neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT 
      depletions can have protracted effects on behavior, suggesting even moderate 
      doses of the drug may pose risks.
FAU - Baumann, Michael H
AU  - Baumann MH
AD  - Clinical Psychopharmacology Section, Intramural Research Program (IRP), National 
      Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 5500 Nathan 
      Shock Drive, Baltimore, MD 21224, USA. mbaumann@intra.nida.nih.gov
FAU - Wang, Xiaoying
AU  - Wang X
FAU - Rothman, Richard B
AU  - Rothman RB
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20060316
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Hallucinogens)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Anxiety/chemically induced
MH  - Behavior, Animal/*drug effects
MH  - Biogenic Monoamines/*metabolism
MH  - Brain/*drug effects/metabolism/pathology
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Hallucinogens/*toxicity
MH  - Humans
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Neurotoxicity Syndromes/*etiology/metabolism/pathology/psychology
MH  - Norepinephrine/metabolism
MH  - Rats
MH  - Risk Assessment
MH  - Serotonin/metabolism
MH  - Species Specificity
PMC - PMC1705495
EDAT- 2006/03/17 09:00
MHDA- 2007/03/03 09:00
PMCR- 2006/03/16
CRDT- 2006/03/17 09:00
PHST- 2005/12/09 00:00 [received]
PHST- 2006/01/07 00:00 [accepted]
PHST- 2006/03/17 09:00 [pubmed]
PHST- 2007/03/03 09:00 [medline]
PHST- 2006/03/17 09:00 [entrez]
PHST- 2006/03/16 00:00 [pmc-release]
AID - 322 [pii]
AID - 10.1007/s00213-006-0322-6 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2007 Jan;189(4):407-24. doi: 
      10.1007/s00213-006-0322-6. Epub 2006 Mar 16.