Withdrawal from amphetamine as an animal model of schizophrenia

D. Peleg-Raibstein, J. Feldon

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

This reviewIn this chapter, I discuss current attempts presents an attempt to develop an animal model of some aspects of schizophrenia directly derived from the =endogenous dopamine sensitization' hypothesis of this disorder. The establishment of the model consists of examination of behavioral, neurochemical and neuroanatomical consequences of various repeated amphetamine administration schedules. These schedules are known to produce behavioral sensitization as is argued to be the case in non-medicated first episode schizophrenics in which their impact is studied during withdrawal from drug administration in the absence of a drug challenge. Evidence demonstrates that during withdrawal deficits in latent inhibition (LI) and pre-pulse inhibition (PPI), two translational phenomena disrupted in schizophrenia, can be reinstated following treatment with both typical and atypical antipsychotic drugs. In addition, the model demonstrates that indeed the treated animals exhibit augmented locomotor activity in response to a challenge injection of amphetamine. Furthermore, withdrawal from amphetamine leads to cognitive deficits in attentional set shifting, working memory, and visual-spatial attention similarly to what is observed in schizophrenic patients. In conclusion, it is suggested that amphetamine withdrawal constitutes a highly valuable animal model of schizophrenia with face, construct, and predictive validity.

Original languageEnglish
Title of host publicationAmphetamines
Subtitle of host publicationNeurobiological Mechanisms, Pharmacology and Effects
PublisherNova Science Publishers, Inc.
Pages119-138
Number of pages20
ISBN (Print)9781614703051
StatePublished - Mar 2012
Externally publishedYes

Keywords

  • Amphetamine
  • Animal model
  • Latent inhibition
  • Pre-pulse inhibition
  • Schizophrenia
  • Sensitization
  • Withdrawal

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