Behavioral consequences of NMDA antagonist-induced neuroapoptosis in the infant mouse brain.
BACKGROUND
Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia.


RESULTS
We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7.


CONCLUSIONS
These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathological and neurobehavioral consequences than a single treatment.
Yuede
Carla M
CM
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America. yuedec@psychiatry.wustl.edu
Wozniak
David F
DF
Creeley
Catherine E
CE
Taylor
George T
GT
Olney
John W
JW
Farber
Nuri B
NB
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D003214:Conditioning, Classical; D005239:Fear; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010622:Phencyclidine / Q000494:pharmacology; D013216:Reflex, Startle
D016202:N-Methylaspartate; D010622:Phencyclidine