Dopamine-Induced Behavioral Changes and Oxidative Stress in Methamphetamine-Induced Neurotoxicity

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

Research output: Contribution to journalReview articlepeer-review

59 Citations (Scopus)


High-dose administration of amphetamine-like compounds is associated with acute behavioral toxicity (including stereotypic and self-injurious behavior and schizophrenic-like psychoses) as well as long-lasting damage to dopaminergic neurons. Several mechanisms are thought to be responsible for methamphetamine-induced neurotoxicity including the formation of reactive oxygen species, dopamine quinones, glutamatergic activity, apoptosis, etc. Recently, new factors regarding glial cell line-derived neurotorophic factor, tumor necrosis factor-α, and interferon-γ have also been associated with methamphetamine-induced neurotoxicity. The objective of this review is to link the behavioral and neurotoxic responses of the amphetamines, emphasizing their common underlying mechanism of monoaminergic release together with inhibition of monoamine oxidase activity. The amphetamine-induced release of dopamine and inhibition of monoamine oxidase increases both cytosolic and synaptic levels of dopamine leading to the acute manifestation of stereotypic and self-injurious behavior. In turn, the enhanced extravesicular levels of dopamine lead to oxidative stress through the generation of reactive oxygen species and dopamine quinones, and cause the long-lasting neuronal damage. Thus, we propose that acute behavioral observation of subjects immediately following methamphetamine administration may provide insight into the long-lasting toxicity to dopaminergic neurons.

Original languageEnglish
Pages (from-to)43-64
Number of pages22
JournalInternational Review of Neurobiology
Issue numberC
Publication statusPublished - 2009


  • Dopamine
  • Methamphetamine
  • Neurotoxicity
  • Self-injurious behavior
  • Sensitization

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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