Differential role of N-methyl-D-aspartate receptor subunits 2A and 2B in mediating phencyclidine-induced perinatal neuronal apoptosis and behavioral deficits

Noelle Anastasio, Y. Xia, Z. R. O'connor, K. M. Johnson

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 PCPinduced apoptosis and the development of long-lasting behavioral deficits.

Original languageEnglish (US)
Pages (from-to)1181-1191
Number of pages11
JournalNeuroscience
Volume163
Issue number4
DOIs
StatePublished - Nov 2009

Fingerprint

Phencyclidine
N-Methyl-D-Aspartate Receptors
Apoptosis
Caspase 3
Corpus Striatum
Sprague Dawley Rats
Schizophrenia
ifenprodil

Keywords

  • Apoptosis
  • Locomotor sensitization
  • N-methyl-D-aspartate receptor
  • Phencyclidine
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential role of N-methyl-D-aspartate receptor subunits 2A and 2B in mediating phencyclidine-induced perinatal neuronal apoptosis and behavioral deficits. / Anastasio, Noelle; Xia, Y.; O'connor, Z. R.; Johnson, K. M.

In: Neuroscience, Vol. 163, No. 4, 11.2009, p. 1181-1191.

Research output: Contribution to journalArticle

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