Aug 2, 2003

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

Journal of Pharmacological Sciences
Taizo KitaT Nakashima

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 ne...Continue Reading

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References

  • References133
  • Citations98

Citations

Mentioned in this Paper

Striatonigral Degeneration, Infantile (Disorder)
Neostriatum
Serotonin Measurement
Caspase-3
Serotonin
Synaptic Vesicles
BCL2 gene
Methamphetamine Measurement
Oxidative Stress
Oxidative Stress Analysis

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