Pharmacological challenge reveals long-term effects of perinatal phencyclidine on delayed spatial alternation in rats

Jenny L. Wiley, Katriona G. Bühler, Kari L. Lavecchia, Kenneth M. Johnson

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Administration of the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP) may produce alterations in behavior that resemble those that have been observed in animal models of schizophrenia. This study was designed to examine the effects of early postnatal injection of PCP on later acquisition and performance of a delayed spatial alternation task, a procedure that is sensitive to manipulations of the prefrontal cortex. At the beginning of the study, we injected cross-fostered female rat pups subcutaneously with either saline or 10 mg/kg PCP on postnatal (PN) days 7, 9, and 11. On PN34, the rats began training in a delayed spatial alternation task consisting of 10 daily trials with a 10-s intertrial interval. Although accuracy improved significantly faster in the saline-treated group than in the PCP-treated group, by PN70, both groups had acquired the task with approximately equal accuracies. Pharmacological challenges with the NMDA antagonists, PCP and ketamine, and with the dopamine modulator, amphetamine, decreased accuracy to a similar extent in both groups of rats when intertrial delays were held constant at 10 s; however, nicotine did not decrease accuracy in either group. In contrast, dizocilpine (a high-affinity NMDA open-channel blocker) produced a more pronounced decrease in accuracy in the PCP-treated rats than in the saline-treated rats. When delays were lengthened to 30 s, PCP also decreased accuracy in the PCP-treated rats to a greater extent than in saline-treated rats. These results suggest that perinatal administration of PCP may produce long-term alterations in cognition that are revealed by pharmacological challenge and manipulation of task difficulty.

Original languageEnglish (US)
Pages (from-to)867-873
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume27
Issue number5
DOIs
StatePublished - Aug 2003

Keywords

  • Amphetamine
  • Dizocilpine
  • Glutamate
  • Phencyclidine
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Pharmacological challenge reveals long-term effects of perinatal phencyclidine on delayed spatial alternation in rats'. Together they form a unique fingerprint.

  • Cite this