Atypical anti-schizophrenic drugs prevent changes in cortical N-methyl-d-aspartate receptors and behavior following sub-chronic phencyclidine administration in developing rat pups

Noelle Anastasio, Kenneth M. Johnson

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21 Citations (Scopus)

Abstract

We sought to determine the relationship between phencyclidine (PCP)-induced alterations in behavior and NMDAR expression in the cortex by examining the effect of anti-schizophrenic drug treatment on both. Sprague-Dawley rat pups were pretreated with risperidone or olanzapine prior to treatment with PCP on postnatal day 7 (PN7) or sub-chronically on PN7, 9, and 11. Pre-pulse inhibition (PPI) of acoustic startle was measured on PN24-26 and following a challenge dose of 4 mg/kg PCP, locomotor activity was measured on PN28-35. PCP treatment on PN7 did not cause a deficit in PPI, but did cause locomotor sensitization. This was prevented by both antipsychotics. PCP treatment on PN7 caused an up-regulation of NR1 and NR2B, which was not affected by either anti-schizophrenic drug. PCP treatment on PN7, 9, and 11 caused a deficit in PPI and a sensitized locomotor response to PCP challenge as well as an up-regulation of NR1 and NR2A, all of which were prevented by both atypical anti-schizophrenic drugs. These data support the hypothesis that sub-chronic, but not single injection PCP treatment in developing rats results in behavioral alterations that are sensitive to antipsychotic drugs and these behavioral changes observed could be related to up-regulation of cortical NR1/NR2A receptors.

Original languageEnglish (US)
Pages (from-to)569-577
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume90
Issue number4
DOIs
StatePublished - Oct 2008

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Phencyclidine
olanzapine
Antipsychotic Agents
Rats
Drug therapy
Risperidone
Pharmaceutical Preparations
Up-Regulation
Acoustics
Therapeutics
Locomotion
Sprague Dawley Rats
aspartic acid receptor
Injections
Inhibition (Psychology)

Keywords

  • Behavioral sensitization
  • Locomotor activity
  • NMDA receptor
  • Olanzapine
  • Phencyclidine
  • Pre-pulse inhibition
  • Risperidone

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

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abstract = "We sought to determine the relationship between phencyclidine (PCP)-induced alterations in behavior and NMDAR expression in the cortex by examining the effect of anti-schizophrenic drug treatment on both. Sprague-Dawley rat pups were pretreated with risperidone or olanzapine prior to treatment with PCP on postnatal day 7 (PN7) or sub-chronically on PN7, 9, and 11. Pre-pulse inhibition (PPI) of acoustic startle was measured on PN24-26 and following a challenge dose of 4 mg/kg PCP, locomotor activity was measured on PN28-35. PCP treatment on PN7 did not cause a deficit in PPI, but did cause locomotor sensitization. This was prevented by both antipsychotics. PCP treatment on PN7 caused an up-regulation of NR1 and NR2B, which was not affected by either anti-schizophrenic drug. PCP treatment on PN7, 9, and 11 caused a deficit in PPI and a sensitized locomotor response to PCP challenge as well as an up-regulation of NR1 and NR2A, all of which were prevented by both atypical anti-schizophrenic drugs. These data support the hypothesis that sub-chronic, but not single injection PCP treatment in developing rats results in behavioral alterations that are sensitive to antipsychotic drugs and these behavioral changes observed could be related to up-regulation of cortical NR1/NR2A receptors.",
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