AGE-SPECIFIC NEUROTOXICITY IN THE RAT ASSOCIATED WITH NMDA RECEPTOR BLOCKADE - POTENTIAL RELEVANCE TO SCHIZOPHRENIA

Agents that block the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor induce a schizophrenialike psychosis in adult humans and inj ure or kill neurons in several corticolimbic regions of the adult rat brain. Susceptibility to the psychotomimetic effects of the NMDA antag onist, ketamine is minimal or absent in children and becomes maximal i n early adulthood, We examined the sensitivity of rats at various ages to the neurotoxic effects of the powerful NMDA antagonist, MK-801. Vu lnerability was found to be age dependent, having onset at approximate ly puberty (45 days of age) and becoming maximal in early adulthood. T his age-dependency profile (onset of susceptibility in late adolescenc e) in the mt is similar to that for ketamine-induced psychosis or schi zophrenia in humans, These findings suggest that NMDA receptor hypofun ction, the mechanism underlying the neurotoxic and psychotomimetic act ions of NMDA antagonists, may also play a role in schizophrenia.