New perspectives on the mechanism of methamphetamine-induced neurotoxicity

Taizo Kita, Mika Takeshima, George C. Wagner, Hiroaki Hozumi, Ikuko Miyazaki, Masato Asanuma

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)


Various hypotheses have been proposed concerning the mechanisms responsible for methamphetamine (METH)-induced neurotoxicity including reactive oxygen species (ROS), dopamine quinones, glutamatergic activity, apoptosis, etc. Recently, new factors regarding glial cell line-derived neurotorophic factor, tumor necrosis factor-α, and α-synuclein contained in striatal interneural inclusions have also been associated with METH-induced neurotoxicity. In addition, METH-induced self-injurious behavior (SIB) has been proposed to be an acute or immediate behavioral marker predicting the long-lasting neurotoxicity induced by METH. Specifically, it has been proposed that the SIB response may accurately reflect the underlying mechanistic changes occurring in the neuron that eventually result in the long-lasting damage. Several studies have demonstrated that endogenous dopamine (DA) plays an important role in mediating METH-induced neuronal damage. DA release and redistribution from synaptic vesicles to cytoplasmic compartments is thought to involve METH-induced changes in both the vesicular monoamine transporter-2 and DA transporter function. In turn, the consequent elevation of cytosolic auto-oxidizable DA concentrations is thought generate ROS such as superoxide and hydroxyl radicals and cause the DA terminal injury. Finally, the inflammatory response of microglia and glutamatergic toxicity in astrocytes have been related to the METH-induced neurotoxicity. The objective of the present review will be to consolidate the new perspectives in an attempt to formulate a more cohesive explanation of the underlying mechanism responsible for METH-induced DA damage and its early biological markers.

Original languageEnglish
Pages (from-to)49-61
Number of pages13
JournalJapanese Journal of Neuropsychopharmacology
Issue number2
Publication statusPublished - Apr 2008


  • Cytokine
  • Dopaminequione
  • Methamphetamine
  • Neurotoxicity
  • Self-injurious behavior

ASJC Scopus subject areas

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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