Dissociation of acute and chronic intermittent phencyclidine-induced performance deficits in the 5-choice serial reaction time task: influence of clozapine

David M Thomson, Allan McVie, Brian J Morris, Judith A Pratt

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cognitive deficits are a core feature of schizophrenia that respond minimally to existing drugs. PCP is commonly used to model schizophrenia-like deficits preclinically although different dosing protocols may affect different domains. Here we characterise the acute, and chronic intermittent effects of PCP in the 5-choice serial reaction time task (5-CSRTT) in rats, and assess the effects of clozapine. In a novel approach, we also assess the effects of increased inhibitory load and conduct clinically relevant signal detection analysis (SDA). The effects of acute and repeated PCP (2.58 mg/kg) treatment on attentional processes and inhibitory control were assessed during and following the chronic treatment regime in the presence or absence of chronic clozapine (20 mg/kg/day). Thirty minutes post-PCP injection, there was an increase in anticipatory responding which disappeared after 24 h. Although, acute PCP did not change accuracy of responding or processing speed, repeated PCP revealed delayed deficits in cognitive processing speed which were partly ameliorated by clozapine. Extended inter-trial intervals increased premature responding, while SDA revealed that clozapine modified persistent PCP-induced deficits in lnBeta (a composite measure of risk taking versus caution). Acute NMDA receptor antagonism impairs inhibitory control, whereas repeated treatment produces delayed deficits in cognitive processing speed. The ability of clozapine partially to restore persistent PCP-induced deficits in processing speed and in lnBeta is consistent with clinical findings. This suggests that the enduring effects of repeated PCP treatment, combined with SDA, offers a useful, translational, approach to evaluate novel cognitive enhancers in the 5-CSRTT.
Original languageEnglish
Pages (from-to)681-95
Number of pages15
JournalPsychopharmacology
Volume213
Issue number4
DOIs
Publication statusPublished - 2011

Fingerprint

Phencyclidine
Clozapine
Reaction Time
Schizophrenia
Nootropic Agents
Aptitude
Therapeutics
Risk-Taking
N-Methyl-D-Aspartate Receptors
Injections
Pharmaceutical Preparations
Psychological Signal Detection

Keywords

  • antipsychotic
  • attention
  • clozapine
  • cognitive
  • cognition
  • delayed response
  • NMDA receptor

Cite this

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title = "Dissociation of acute and chronic intermittent phencyclidine-induced performance deficits in the 5-choice serial reaction time task: influence of clozapine",
abstract = "Cognitive deficits are a core feature of schizophrenia that respond minimally to existing drugs. PCP is commonly used to model schizophrenia-like deficits preclinically although different dosing protocols may affect different domains. Here we characterise the acute, and chronic intermittent effects of PCP in the 5-choice serial reaction time task (5-CSRTT) in rats, and assess the effects of clozapine. In a novel approach, we also assess the effects of increased inhibitory load and conduct clinically relevant signal detection analysis (SDA). The effects of acute and repeated PCP (2.58 mg/kg) treatment on attentional processes and inhibitory control were assessed during and following the chronic treatment regime in the presence or absence of chronic clozapine (20 mg/kg/day). Thirty minutes post-PCP injection, there was an increase in anticipatory responding which disappeared after 24 h. Although, acute PCP did not change accuracy of responding or processing speed, repeated PCP revealed delayed deficits in cognitive processing speed which were partly ameliorated by clozapine. Extended inter-trial intervals increased premature responding, while SDA revealed that clozapine modified persistent PCP-induced deficits in lnBeta (a composite measure of risk taking versus caution). Acute NMDA receptor antagonism impairs inhibitory control, whereas repeated treatment produces delayed deficits in cognitive processing speed. The ability of clozapine partially to restore persistent PCP-induced deficits in processing speed and in lnBeta is consistent with clinical findings. This suggests that the enduring effects of repeated PCP treatment, combined with SDA, offers a useful, translational, approach to evaluate novel cognitive enhancers in the 5-CSRTT.",
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Dissociation of acute and chronic intermittent phencyclidine-induced performance deficits in the 5-choice serial reaction time task: influence of clozapine. / Thomson, David M; McVie, Allan; Morris, Brian J; Pratt, Judith A.

In: Psychopharmacology, Vol. 213, No. 4, 2011, p. 681-95.

Research output: Contribution to journalArticle

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