Current understanding of methamphetamine-associated dopaminergic neurodegeneration and psychotoxic behaviors

Arch Pharm Res. 2017 Apr;40(4):403-428. doi: 10.1007/s12272-017-0897-y. Epub 2017 Feb 28.


Clinical and preclinical studies have indicated that chronic methamphetamine (MA) use is associated with extensive neurodegeneration, psychosis, and cognitive impairment. Evidence from animal models has suggested a considerable role of excess dopamine or glutamate, oxidative stress, neuroinflammation, and apoptosis in MA-induced neurotoxicity, and that protein kinase Cδ might mediate the interaction among these factors. In addition, the relatively long-lasting and recurrent nature of MA psychosis has been reproduced in animals treated with various dosing regimens of MA, which have shown behavioral sensitization, sociability deficits, and impaired prepulse inhibition. Genetic predisposition as well as dopaminergic and glutamatergic alterations might be important in the development of MA psychosis. Neuroimaging studies have identified functional and morphological changes related to the cognitive dysfunction shown in chronic MA users. Failure in the task-evoked phosphorylation of extracellular signal-related kinase likely underlies MA-induced memory impairment. Recent progress has suggested certain roles of oxidative stress and neuroinflammation in the psychosis and cognitive deficits induced by repeated low doses of MA. This review provides a comprehensive description of pertinent findings from human and animal studies, with an emphasis on the current understanding of the underlying mechanisms of MA neuropsychotoxicity and its relevance to Parkinson's disease or schizophrenia.

Keywords: Cognitive impairment; Methamphetamine; Neurotoxicity; Psychosis; Underlying mechanism.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / adverse effects*
  • Central Nervous System Stimulants / metabolism*
  • Dopamine / metabolism*
  • Humans
  • Methamphetamine / administration & dosage
  • Methamphetamine / adverse effects*
  • Methamphetamine / metabolism*


  • Central Nervous System Stimulants
  • Methamphetamine
  • Dopamine