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Differential role of N-methyl-d-aspartate receptor subunits 2A and 2B in mediating phencyclidine-induced perinatal neuronal apoptosis and behavioral deficits
- Source :
-
Neuroscience . Nov2009, Vol. 163 Issue 4, p1181-1191. 11p. - Publication Year :
- 2009
-
Abstract
- Abstract: The mechanism underlying phencyclidine (PCP)-induced apoptosis in perinatal rats and the development of schizophrenia-like behaviors is incompletely understood. We used antagonists for N-methyl-d-aspartate (NMDA) receptor subunit NR2A- and NR2B-containing NMDA receptor to test the hypothesis that the behavioral and apoptotic effects of PCP are mediated by blockade of NR1/NR2A-containing receptors, rather than NR1/NR2B-containing receptors. Sprague-Dawley rats were treated on PN7, PN9, and PN11 with PCP (10 mg/kg), PEAQX (NR2A-preferring antagonist; 10, 20, or 40 mg/kg), or ifenprodil (selective NR2B antagonist; 1, 5, or 10 mg/kg) and sacrificed for measurement of caspase-3 activity (an index of apoptosis) or allowed to age and tested for locomotor sensitization to PCP challenge on PN28-PN35. PCP or PEAQX on PN7, PN9, and PN11 markedly elevated caspase-3 activity in the cortex; ifenprodil showed no effect. Striatal apoptosis was evident only after subchronic treatment with a high dose of PEAQX (20 mg/kg). Animals treated with PCP or PEAQX on PN7, PN9, and PN11 showed a sensitized locomotor response to PCP challenge on PN28-PN35. Ifenprodil treatment had no effect on either measure. Therefore, PCP blockade of cortical NR1/NR2A, rather than NR1/NR2B, appears to be responsible for PCP-induced apoptosis and the development of long-lasting behavioral deficits. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 163
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 44584704
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2009.07.058