The amphetamine-induced sensitized state as a model of schizophrenia

Prog Neuropsychopharmacol Biol Psychiatry. 2007 Nov 15;31(8):1556-71. doi: 10.1016/j.pnpbp.2007.08.025. Epub 2007 Aug 28.


Schizophrenia is a serious psychiatric disorder which impacts a broad range of cognitive, behavioural and emotional domains. In animals, exposure to an intermittent, escalating dose regimen of amphetamine induces a sensitized state that appears to share a number of behavioural and neurochemical similarities with schizophrenia. In humans repeated exposure to amphetamine, or other psychomotor stimulants, can induce sensitization as well as psychosis. The following paper evaluates the evidence for the amphetamine-induced sensitized state as an animal model of schizophrenia, focussing separately on the positive, cognitive and negative symptoms associated with this disease. Current evidence supports the use of amphetamine sensitization as a model of the positive symptoms observed in schizophrenia. Additionally, there is increasing evidence for long-lasting cognitive deficits in sensitized animals, especially in the area of attention and/or cognitive flexibility. Other areas of cognition, such as long-term memory, appear to be unaltered in sensitized animals. Finally, little evidence currently exists to either support or refute the use of amphetamine sensitization as a model of negative symptoms. It is concluded that amphetamine sensitization likely impacts behaviour by altering the functioning of mesolimbic dopamine systems and prefrontal cortical function and can serve as a model of certain domains of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamine / toxicity*
  • Animals
  • Brain / pathology
  • Brain Chemistry / physiology
  • Central Nervous System Stimulants / toxicity*
  • Cognition Disorders / physiopathology
  • Disease Models, Animal
  • Dopamine / physiology
  • Humans
  • Schizophrenia / chemically induced*
  • Schizophrenia / pathology
  • Schizophrenic Psychology
  • Substance-Related Disorders / psychology


  • Central Nervous System Stimulants
  • Amphetamine
  • Dopamine