TY - JOUR
T1 - Age-specific neurotoxicity in the rat associated with NMDA receptor blockade
T2 - Potential relevance to schizophrenia?
AU - Farber, Nuri B.
AU - Wozniak, David F.
AU - Price, Madelon T.
AU - Labruyere, Joann
AU - Huss, Janice
AU - St. Peter, Heidi
AU - Olney, John W.
PY - 1995/12/15
Y1 - 1995/12/15
N2 - 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.
AB - 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.
KW - MK-801 (dizocilipine)
KW - NMDA antagonist neurotoxicity
KW - Posterior cingulate and retrosplenial cortices
KW - age-dependent susceptibility
KW - emergence reaction
KW - psychosis
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=0029646097&partnerID=8YFLogxK
U2 - 10.1016/0006-3223(95)00046-1
DO - 10.1016/0006-3223(95)00046-1
M3 - Article
C2 - 8750036
AN - SCOPUS:0029646097
SN - 0006-3223
VL - 38
SP - 788
EP - 796
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 12
ER -