Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy")

Science. 2002 Sep 27;297(5590):2260-3. doi: 10.1126/science.1074501.

Abstract

The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy") is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Autoradiography
  • Axons / drug effects
  • Axons / metabolism
  • Axons / ultrastructure
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / ultrastructure
  • Carrier Proteins / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / ultrastructure
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Hallucinogens / administration & dosage
  • Hallucinogens / adverse effects
  • Hallucinogens / toxicity*
  • Humans
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / metabolism
  • Motor Activity / drug effects
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage
  • N-Methyl-3,4-methylenedioxyamphetamine / adverse effects
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Nerve Degeneration
  • Nerve Tissue Proteins*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Norepinephrine / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins
  • Papio
  • Parkinsonian Disorders / chemically induced
  • Saimiri
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Symporters / metabolism
  • Tremor / chemically induced
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Hallucinogens
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • SLC6A2 protein, human
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Symporters
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tyrosine 3-Monooxygenase
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Dopamine
  • Norepinephrine