Age-specific neurotoxicity in the rat associated with NMDA receptor blockade: Potential relevance to schizophrenia?

Nuri B. Farber, David F. Wozniak, Madelon T. Price, Joann Labruyere, Janice Huss, Heidi St. Peter, John W. Olney

Research output: Contribution to journalArticlepeer-review

200 Scopus citations


Agents that block the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor induce a schizophrenialike psychosis in adult humans and injure or kill neurons in several corticolimbic regions of the adult rat brain. Susceptibility to the psychotomimetic effects of the NMDA antagonist, ketamine is minimal or absent in children and becomes maximal in early adulthood. We examined the sensitivity of rats at various ages to the neurotoxic effects of the powerful NMDA antagonist, MK-801. Vulnerability was found to be age dependent, having onset at approximately puberty (45 days of age) and becoming maximal in early adulthood. This age-dependency profile (onset of susceptibility in late adolescence) in the rat is similar to that for ketamine-induced psychosis or schizophrenia in humans. These findings suggest that NMDA receptor hypofunction, the mechanism underlying the neurotoxic and psychotomimetic actions of NMDA antagonists, may also play a role in schizophrenia.

Original languageEnglish
Pages (from-to)788-796
Number of pages9
JournalBiological Psychiatry
Issue number12
StatePublished - Dec 15 1995


  • MK-801 (dizocilipine)
  • NMDA antagonist neurotoxicity
  • Posterior cingulate and retrosplenial cortices
  • age-dependent susceptibility
  • emergence reaction
  • psychosis
  • schizophrenia


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