Noradrenergic loss enhances MDMA toxicity and induces ubiquitin-positive striatal whorls

Neurol Sci. 2002 Sep:23 Suppl 2:S75-6. doi: 10.1007/s100720200077.

Abstract

Movement disorders involve a number of neurodegenerative conditions, mostly affecting basal ganglia. Parkinson's disease (PD) is classically defined by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Administration of specific neurotoxins represents a common tool to reproduce this lesion. Among these, amphetamine derivatives act as powerful monoamine neurotoxins, impairing striatal dopamine (DA) axons in mice. Despite the well-investigated effects on striatal DA terminals, only sporadic studies have focused on the potential toxicity of amphetamines towards post-synaptic neurons within the striatum. In the present work we found that 3,4-methylenedioxymethamphetamine (MDMA) produces ultrastructural alterations in striatal cells, featuring as membraneous whorls, positive for ubiquitin and heat shock protein 70. These morphological alterations were enhanced in locus coeruleus-lesioned mice.

MeSH terms

  • Adrenergic Uptake Inhibitors / toxicity*
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • HSP70 Heat-Shock Proteins / metabolism
  • Locus Coeruleus / surgery
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Neurons / diagnostic imaging
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Norepinephrine / deficiency*
  • Ubiquitin / metabolism*
  • Ultrasonography

Substances

  • Adrenergic Uptake Inhibitors
  • HSP70 Heat-Shock Proteins
  • Ubiquitin
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Norepinephrine