Current research on methamphetamine-induced neurotoxicity: Animal models of monoamine disruption

Taizo Kita, George C. Wagner, Toshikatsu Nakashima

Research output: Contribution to journalReview articlepeer-review

145 Scopus citations

Abstract

Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)178-195
Number of pages18
JournalJournal of Pharmacological Sciences
Volume92
Issue number3
DOIs
StatePublished - Jul 1 2003

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Keywords

  • Apoptosis
  • Dopamine
  • Free-radical
  • Methamphetamine
  • Neurotoxicity

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