Behavioral consequences of NMDA antagonist-induced neuroapoptosis in the infant mouse brain.

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Yuede CM, Wozniak DF, Creeley CE, Taylor GT, Olney JW, Farber NB

Behavioral consequences of NMDA antagonist-induced neuroapoptosis in the infant mouse brain.

PLoS One. 2010 Jun 29;5(6):e11374. doi: 10.1371/journal.pone.0011374.

PubMed ID

20613880 [ View in PubMed

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Abstract

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. METHODOLOGY/PRINCIPAL FINDINGS: 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Rolicyclidine	Glutamate receptor ionotropic, NMDA 3A	Protein	Humans	Yes	Not Available	Details