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3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings.
Psychopharmacology (Berl). 2007 Jan; 189(4):407-24.P

Abstract

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.

Authors+Show Affiliations

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.govNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

16541247

Citation

Baumann, Michael H., et al. "3,4-Methylenedioxymethamphetamine (MDMA) Neurotoxicity in Rats: a Reappraisal of Past and Present Findings." Psychopharmacology, vol. 189, no. 4, 2007, pp. 407-24.
Baumann MH, Wang X, Rothman RB. 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacology (Berl). 2007;189(4):407-24.
Baumann, M. H., Wang, X., & Rothman, R. B. (2007). 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacology, 189(4), 407-24.
Baumann MH, Wang X, Rothman RB. 3,4-Methylenedioxymethamphetamine (MDMA) Neurotoxicity in Rats: a Reappraisal of Past and Present Findings. Psychopharmacology (Berl). 2007;189(4):407-24. PubMed PMID: 16541247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. AU - Baumann,Michael H, AU - Wang,Xiaoying, AU - Rothman,Richard B, Y1 - 2006/03/16/ PY - 2005/12/09/received PY - 2006/01/07/accepted PY - 2006/3/17/pubmed PY - 2007/3/3/medline PY - 2006/3/17/entrez SP - 407 EP - 24 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 189 IS - 4 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/16541247/34_Methylenedioxymethamphetamine__MDMA__neurotoxicity_in_rats:_a_reappraisal_of_past_and_present_findings_ L2 - https://dx.doi.org/10.1007/s00213-006-0322-6 DB - PRIME DP - Unbound Medicine ER -