Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats

Alice Egerton, Lee Reid, Sandie McGregor, Susan M. Cochran, Brian J. Morris, Judith Pratt

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003). We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes. Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine. Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction. The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.
LanguageEnglish
Pages37-49
Number of pages13
JournalPsychopharmacology
Volume198
Issue number1
DOIs
Publication statusPublished - Apr 2008

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Schizophrenia
Aptitude
Amphetamine
Interpersonal Relations
N-Methyl-D-Aspartate Receptors
Locomotion
Prefrontal Cortex
Pathology
Prepulse Inhibition

Keywords

  • phencyclidine
  • attentional set-shifting
  • prepulse inhibition
  • schizophrenia
  • prefrontal cortex
  • social interaction

Cite this

Egerton, Alice ; Reid, Lee ; McGregor, Sandie ; Cochran, Susan M. ; Morris, Brian J. ; Pratt, Judith. / Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats. In: Psychopharmacology. 2008 ; Vol. 198, No. 1. pp. 37-49.
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Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats. / Egerton, Alice; Reid, Lee; McGregor, Sandie; Cochran, Susan M.; Morris, Brian J.; Pratt, Judith.

In: Psychopharmacology, Vol. 198, No. 1, 04.2008, p. 37-49.

Research output: Contribution to journalArticle

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AU - Reid, Lee

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